PubMed:23811795 JSONTXT

{"project":"Glycan-Motif","denotations":[{"id":"T1","span":{"begin":762,"end":782},"obj":"https://glytoucan.org/Structures/Glycans/G64581RP"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":762,"end":782},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G64581RP"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":762,"end":782},"obj":"https://glytoucan.org/Structures/Glycans/G64581RP"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

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{"project":"GlycoBiology-GDGDB","denotations":[{"id":"_T1","span":{"begin":709,"end":722},"obj":"http://acgg.asia/db/diseases/gdgdb?con_ui=CON00008"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

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V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"uniprot-mouse","denotations":[{"id":"T1","span":{"begin":0,"end":31},"obj":"http://www.uniprot.org/uniprot/P97402"},{"id":"T2","span":{"begin":150,"end":181},"obj":"http://www.uniprot.org/uniprot/P97402"},{"id":"T3","span":{"begin":812,"end":815},"obj":"http://www.uniprot.org/uniprot/P42867"},{"id":"T4","span":{"begin":886,"end":889},"obj":"http://www.uniprot.org/uniprot/P63028"},{"id":"T5","span":{"begin":886,"end":889},"obj":"http://www.uniprot.org/uniprot/Q62092"},{"id":"T6","span":{"begin":886,"end":889},"obj":"http://www.uniprot.org/uniprot/P39689"},{"id":"T7","span":{"begin":1293,"end":1316},"obj":"http://www.uniprot.org/uniprot/P01132"},{"id":"T8","span":{"begin":1293,"end":1325},"obj":"http://www.uniprot.org/uniprot/Q01279"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GlycoBiology-NCBITAXON","denotations":[{"id":"T1","span":{"begin":51,"end":56},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T2","span":{"begin":210,"end":219},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/166034"},{"id":"T3","span":{"begin":244,"end":249},"obj":"http://purl.bioontology.org/ontology/STY/T051"},{"id":"T4","span":{"begin":370,"end":379},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/127244"},{"id":"T5","span":{"begin":612,"end":617},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T6","span":{"begin":1169,"end":1174},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T7","span":{"begin":1345,"end":1350},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T8","span":{"begin":1583,"end":1588},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T9","span":{"begin":1859,"end":1864},"obj":"http://purl.bioontology.org/ontology/STY/T051"},{"id":"T10","span":{"begin":1913,"end":1918},"obj":"http://purl.bioontology.org/ontology/STY/T025"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GO-BP","denotations":[{"id":"T1","span":{"begin":0,"end":33},"obj":"http://purl.obolibrary.org/obo/GO_0030144"},{"id":"T2","span":{"begin":138,"end":183},"obj":"http://purl.obolibrary.org/obo/GO_0030144"},{"id":"T3","span":{"begin":76,"end":83},"obj":"http://purl.obolibrary.org/obo/GO_0043276"},{"id":"T4","span":{"begin":592,"end":599},"obj":"http://purl.obolibrary.org/obo/GO_0043276"},{"id":"T5","span":{"begin":1118,"end":1125},"obj":"http://purl.obolibrary.org/obo/GO_0043276"},{"id":"T6","span":{"begin":1454,"end":1461},"obj":"http://purl.obolibrary.org/obo/GO_0043276"},{"id":"T7","span":{"begin":1649,"end":1656},"obj":"http://purl.obolibrary.org/obo/GO_0043276"},{"id":"T8","span":{"begin":1882,"end":1889},"obj":"http://purl.obolibrary.org/obo/GO_0043276"},{"id":"T9","span":{"begin":92,"end":96},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T10","span":{"begin":1327,"end":1331},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T11","span":{"begin":1352,"end":1356},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T12","span":{"begin":1629,"end":1633},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T13","span":{"begin":1814,"end":1818},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T14","span":{"begin":1983,"end":1987},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T15","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0047222"},{"id":"T16","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0008454"},{"id":"T17","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0008455"},{"id":"T18","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0047261"},{"id":"T19","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0008917"},{"id":"T20","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0017176"},{"id":"T21","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0001888"},{"id":"T22","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0003829"},{"id":"T23","span":{"begin":138,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0008109"},{"id":"T24","span":{"begin":422,"end":431},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T25","span":{"begin":422,"end":439},"obj":"http://purl.obolibrary.org/obo/GO_0007165"},{"id":"T26","span":{"begin":571,"end":577},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T27","span":{"begin":1303,"end":1309},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T28","span":{"begin":1443,"end":1449},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T29","span":{"begin":571,"end":591},"obj":"http://purl.obolibrary.org/obo/GO_0045926"},{"id":"T30","span":{"begin":812,"end":815},"obj":"http://purl.obolibrary.org/obo/GO_0004021"},{"id":"T31","span":{"begin":890,"end":906},"obj":"http://purl.obolibrary.org/obo/GO_0033674"},{"id":"T32","span":{"begin":1061,"end":1077},"obj":"http://purl.obolibrary.org/obo/GO_0033674"},{"id":"T33","span":{"begin":890,"end":906},"obj":"http://purl.obolibrary.org/obo/GO_0016301"},{"id":"T34","span":{"begin":1061,"end":1077},"obj":"http://purl.obolibrary.org/obo/GO_0016301"},{"id":"T35","span":{"begin":890,"end":908},"obj":"http://purl.obolibrary.org/obo/GO_0050254"},{"id":"T36","span":{"begin":890,"end":908},"obj":"http://purl.obolibrary.org/obo/GO_0052835"},{"id":"T37","span":{"begin":890,"end":908},"obj":"http://purl.obolibrary.org/obo/GO_0004707"},{"id":"T38","span":{"begin":890,"end":908},"obj":"http://purl.obolibrary.org/obo/GO_0004715"},{"id":"T39","span":{"begin":890,"end":908},"obj":"http://purl.obolibrary.org/obo/GO_0019140"},{"id":"T40","span":{"begin":890,"end":908},"obj":"http://purl.obolibrary.org/obo/GO_0047944"},{"id":"T41","span":{"begin":1061,"end":1087},"obj":"http://purl.obolibrary.org/obo/GO_0004860"},{"id":"T42","span":{"begin":1061,"end":1087},"obj":"http://purl.obolibrary.org/obo/GO_0008384"},{"id":"T43","span":{"begin":1061,"end":1087},"obj":"http://purl.obolibrary.org/obo/GO_0007249"},{"id":"T44","span":{"begin":1061,"end":1087},"obj":"http://purl.obolibrary.org/obo/GO_0019210"},{"id":"T45","span":{"begin":1071,"end":1087},"obj":"http://purl.obolibrary.org/obo/GO_0033673"},{"id":"T46","span":{"begin":1366,"end":1383},"obj":"http://purl.obolibrary.org/obo/GO_0033673"},{"id":"T47","span":{"begin":1246,"end":1259},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T48","span":{"begin":1772,"end":1785},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T49","span":{"begin":1274,"end":1289},"obj":"http://purl.obolibrary.org/obo/GO_0016310"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GO-MF","denotations":[{"id":"T1","span":{"begin":1303,"end":1325},"obj":"http://purl.obolibrary.org/obo/GO_0070851"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GO-CC","denotations":[{"id":"T1","span":{"begin":51,"end":56},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2","span":{"begin":612,"end":617},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T3","span":{"begin":1169,"end":1174},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T4","span":{"begin":1345,"end":1350},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T5","span":{"begin":1583,"end":1588},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T6","span":{"begin":1913,"end":1918},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"Allie","denotations":[{"id":"SS1_23811795_1_0","span":{"begin":195,"end":219},"obj":"expanded"},{"id":"SS2_23811795_1_0","span":{"begin":221,"end":224},"obj":"abbr"},{"id":"SS1_23811795_5_0","span":{"begin":886,"end":908},"obj":"expanded"},{"id":"SS2_23811795_5_0","span":{"begin":910,"end":914},"obj":"abbr"},{"id":"SS1_23811795_6_0","span":{"begin":1293,"end":1325},"obj":"expanded"},{"id":"SS2_23811795_6_0","span":{"begin":1327,"end":1331},"obj":"abbr"}],"relations":[{"id":"AE1_23811795_1_0","pred":"abbreviatedTo","subj":"SS1_23811795_1_0","obj":"SS2_23811795_1_0"},{"id":"AE1_23811795_5_0","pred":"abbreviatedTo","subj":"SS1_23811795_5_0","obj":"SS2_23811795_5_0"},{"id":"AE1_23811795_6_0","pred":"abbreviatedTo","subj":"SS1_23811795_6_0","obj":"SS2_23811795_6_0"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":195,"end":219},"obj":"HP_0001402"},{"id":"T2","span":{"begin":262,"end":267},"obj":"HP_0002664"},{"id":"T3","span":{"begin":997,"end":1001},"obj":"HP_0000365"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"GlyTouCan-IUPAC","denotations":[{"id":"GlycanIUPAC_T1","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G26693XF\""},{"id":"GlycanIUPAC_T2","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G26693XF\""},{"id":"GlycanIUPAC_T3","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G26693XF\""},{"id":"GlycanIUPAC_T4","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G01864SU\""},{"id":"GlycanIUPAC_T5","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G01864SU\""},{"id":"GlycanIUPAC_T6","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G01864SU\""},{"id":"GlycanIUPAC_T7","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G17605FD\""},{"id":"GlycanIUPAC_T8","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G17605FD\""},{"id":"GlycanIUPAC_T9","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G17605FD\""},{"id":"GlycanIUPAC_T10","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G41950LU\""},{"id":"GlycanIUPAC_T11","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G41950LU\""},{"id":"GlycanIUPAC_T12","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G41950LU\""},{"id":"GlycanIUPAC_T13","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G57195RJ\""},{"id":"GlycanIUPAC_T14","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G57195RJ\""},{"id":"GlycanIUPAC_T15","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G57195RJ\""},{"id":"GlycanIUPAC_T16","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G85391SA\""},{"id":"GlycanIUPAC_T17","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G85391SA\""},{"id":"GlycanIUPAC_T18","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G85391SA\""},{"id":"GlycanIUPAC_T19","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G89565QL\""},{"id":"GlycanIUPAC_T20","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G89565QL\""},{"id":"GlycanIUPAC_T21","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G89565QL\""},{"id":"GlycanIUPAC_T22","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G80869MR\""},{"id":"GlycanIUPAC_T23","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G80869MR\""},{"id":"GlycanIUPAC_T24","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G80869MR\""},{"id":"GlycanIUPAC_T25","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G55978NL\""},{"id":"GlycanIUPAC_T26","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G55978NL\""},{"id":"GlycanIUPAC_T27","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G55978NL\""},{"id":"GlycanIUPAC_T28","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G54644LT\""},{"id":"GlycanIUPAC_T29","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G54644LT\""},{"id":"GlycanIUPAC_T30","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G54644LT\""},{"id":"GlycanIUPAC_T31","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G25694UG\""},{"id":"GlycanIUPAC_T32","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G25694UG\""},{"id":"GlycanIUPAC_T33","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G25694UG\""},{"id":"GlycanIUPAC_T34","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G25126RB\""},{"id":"GlycanIUPAC_T35","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G25126RB\""},{"id":"GlycanIUPAC_T36","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G25126RB\""},{"id":"GlycanIUPAC_T37","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G51848AD\""},{"id":"GlycanIUPAC_T38","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G51848AD\""},{"id":"GlycanIUPAC_T39","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G51848AD\""},{"id":"GlycanIUPAC_T40","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G94667GM\""},{"id":"GlycanIUPAC_T41","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G94667GM\""},{"id":"GlycanIUPAC_T42","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G94667GM\""},{"id":"GlycanIUPAC_T43","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G30124BO\""},{"id":"GlycanIUPAC_T44","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G30124BO\""},{"id":"GlycanIUPAC_T45","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G30124BO\""},{"id":"GlycanIUPAC_T46","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G82777EZ\""},{"id":"GlycanIUPAC_T47","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G82777EZ\""},{"id":"GlycanIUPAC_T48","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G82777EZ\""},{"id":"GlycanIUPAC_T49","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G10151YZ\""},{"id":"GlycanIUPAC_T50","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G10151YZ\""},{"id":"GlycanIUPAC_T51","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G10151YZ\""},{"id":"GlycanIUPAC_T52","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G17585ZM\""},{"id":"GlycanIUPAC_T53","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G17585ZM\""},{"id":"GlycanIUPAC_T54","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G17585ZM\""},{"id":"GlycanIUPAC_T55","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G04411CJ\""},{"id":"GlycanIUPAC_T56","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G04411CJ\""},{"id":"GlycanIUPAC_T57","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G04411CJ\""},{"id":"GlycanIUPAC_T58","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G38254HJ\""},{"id":"GlycanIUPAC_T59","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G38254HJ\""},{"id":"GlycanIUPAC_T60","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G38254HJ\""},{"id":"GlycanIUPAC_T61","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G75188FS\""},{"id":"GlycanIUPAC_T62","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G75188FS\""},{"id":"GlycanIUPAC_T63","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G75188FS\""},{"id":"GlycanIUPAC_T64","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G70374VG\""},{"id":"GlycanIUPAC_T65","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G70374VG\""},{"id":"GlycanIUPAC_T66","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G70374VG\""},{"id":"GlycanIUPAC_T67","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G45176LJ\""},{"id":"GlycanIUPAC_T68","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G45176LJ\""},{"id":"GlycanIUPAC_T69","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G45176LJ\""},{"id":"GlycanIUPAC_T70","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G30874VW\""},{"id":"GlycanIUPAC_T71","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G30874VW\""},{"id":"GlycanIUPAC_T72","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G30874VW\""},{"id":"GlycanIUPAC_T73","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G69333MI\""},{"id":"GlycanIUPAC_T74","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G69333MI\""},{"id":"GlycanIUPAC_T75","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G69333MI\""},{"id":"GlycanIUPAC_T76","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G10676XO\""},{"id":"GlycanIUPAC_T77","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G10676XO\""},{"id":"GlycanIUPAC_T78","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G10676XO\""},{"id":"GlycanIUPAC_T79","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G14843DJ\""},{"id":"GlycanIUPAC_T80","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G14843DJ\""},{"id":"GlycanIUPAC_T81","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G14843DJ\""},{"id":"GlycanIUPAC_T82","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G47546FR\""},{"id":"GlycanIUPAC_T83","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G47546FR\""},{"id":"GlycanIUPAC_T84","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G47546FR\""},{"id":"GlycanIUPAC_T85","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G73695ZM\""},{"id":"GlycanIUPAC_T86","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G73695ZM\""},{"id":"GlycanIUPAC_T87","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G73695ZM\""},{"id":"GlycanIUPAC_T88","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G31923TJ\""},{"id":"GlycanIUPAC_T89","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G31923TJ\""},{"id":"GlycanIUPAC_T90","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G31923TJ\""},{"id":"GlycanIUPAC_T91","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G60519EP\""},{"id":"GlycanIUPAC_T92","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G60519EP\""},{"id":"GlycanIUPAC_T93","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G60519EP\""},{"id":"GlycanIUPAC_T94","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G07933IA\""},{"id":"GlycanIUPAC_T95","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G07933IA\""},{"id":"GlycanIUPAC_T96","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G07933IA\""},{"id":"GlycanIUPAC_T97","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G40745NH\""},{"id":"GlycanIUPAC_T98","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G40745NH\""},{"id":"GlycanIUPAC_T99","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G40745NH\""},{"id":"GlycanIUPAC_T100","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G54496YV\""},{"id":"GlycanIUPAC_T101","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G54496YV\""},{"id":"GlycanIUPAC_T102","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G54496YV\""},{"id":"GlycanIUPAC_T103","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G62953SQ\""},{"id":"GlycanIUPAC_T104","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G62953SQ\""},{"id":"GlycanIUPAC_T105","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G62953SQ\""},{"id":"GlycanIUPAC_T106","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G70070AY\""},{"id":"GlycanIUPAC_T107","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G70070AY\""},{"id":"GlycanIUPAC_T108","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G70070AY\""},{"id":"GlycanIUPAC_T109","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G78792WC\""},{"id":"GlycanIUPAC_T110","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G78792WC\""},{"id":"GlycanIUPAC_T111","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G78792WC\""},{"id":"GlycanIUPAC_T112","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G25238AV\""},{"id":"GlycanIUPAC_T113","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G25238AV\""},{"id":"GlycanIUPAC_T114","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G25238AV\""},{"id":"GlycanIUPAC_T115","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G40510DP\""},{"id":"GlycanIUPAC_T116","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G40510DP\""},{"id":"GlycanIUPAC_T117","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G40510DP\""},{"id":"GlycanIUPAC_T118","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G61120TK\""},{"id":"GlycanIUPAC_T119","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G61120TK\""},{"id":"GlycanIUPAC_T120","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G61120TK\""},{"id":"GlycanIUPAC_T121","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G41342KV\""},{"id":"GlycanIUPAC_T122","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G41342KV\""},{"id":"GlycanIUPAC_T123","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G41342KV\""},{"id":"GlycanIUPAC_T124","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G90703NA\""},{"id":"GlycanIUPAC_T125","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G90703NA\""},{"id":"GlycanIUPAC_T126","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G90703NA\""},{"id":"GlycanIUPAC_T127","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G01591HR\""},{"id":"GlycanIUPAC_T128","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G01591HR\""},{"id":"GlycanIUPAC_T129","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G01591HR\""},{"id":"GlycanIUPAC_T130","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G56520XN\""},{"id":"GlycanIUPAC_T131","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G56520XN\""},{"id":"GlycanIUPAC_T132","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G56520XN\""},{"id":"GlycanIUPAC_T133","span":{"begin":784,"end":790},"obj":"\"http://rdf.glycoinfo.org/glycan/G81830JX\""},{"id":"GlycanIUPAC_T134","span":{"begin":1228,"end":1234},"obj":"\"http://rdf.glycoinfo.org/glycan/G81830JX\""},{"id":"GlycanIUPAC_T135","span":{"begin":1754,"end":1760},"obj":"\"http://rdf.glycoinfo.org/glycan/G81830JX\""}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"NGLY1-deficiency","denotations":[{"id":"PD-NGLY1-deficiency-B_T1","span":{"begin":762,"end":782},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T2","span":{"begin":784,"end":790},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T3","span":{"begin":1228,"end":1234},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T4","span":{"begin":1754,"end":1760},"obj":"chem:24139"}],"namespaces":[{"prefix":"hgnc","uri":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:"},{"prefix":"omim","uri":"https://www.omim.org/entry/"},{"prefix":"chem","uri":"https://pubchem.ncbi.nlm.nih.gov/compound/"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":195,"end":219},"obj":"Phenotype"},{"id":"T2","span":{"begin":221,"end":224},"obj":"Phenotype"},{"id":"T3","span":{"begin":262,"end":267},"obj":"Phenotype"},{"id":"T4","span":{"begin":2061,"end":2064},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0001402"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0001402"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002664"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0001402"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":42,"end":50},"obj":"Disease"},{"id":"T2","span":{"begin":195,"end":219},"obj":"Disease"},{"id":"T3","span":{"begin":221,"end":224},"obj":"Disease"},{"id":"T4","span":{"begin":262,"end":267},"obj":"Disease"},{"id":"T5","span":{"begin":447,"end":455},"obj":"Disease"},{"id":"T6","span":{"begin":603,"end":611},"obj":"Disease"},{"id":"T7","span":{"begin":1160,"end":1168},"obj":"Disease"},{"id":"T8","span":{"begin":1336,"end":1344},"obj":"Disease"},{"id":"T9","span":{"begin":1574,"end":1582},"obj":"Disease"},{"id":"T10","span":{"begin":1904,"end":1912},"obj":"Disease"},{"id":"T11","span":{"begin":2061,"end":2064},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0007256"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":1293,"end":1309},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000021"}],"text":"N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation.\nElevated expression and activity of N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma (HCC) is a common early event involved in tumor invasion during hepatocarcinogenesis. A better understanding of the functional role and the molecular mechanism for Mgat5-targeted protein and downstream signaling pathway behind hepatoma invasion and metastasis is urgently needed. Here, we show that Mgat5 overexpression promoted anchorage-independent growth and inhibited anoikis in hepatoma cells. This effect was reversed by glycosyltransferase inactive mutant Mgat5 L188R transfection, α-mannosidase II inhibitor swainsonine treatment and N-acetyl glucosamine (GlcNAc) phosphotransferase (GPT) inhibitor tunicamycin administration. Mgat5 overexpression increased p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase inactivation with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor P21-activated kinase inhibitor III (IPA3) treatment reversed anoikis resistance in Mgat5-overexpressed hepatoma cells. Furthermore, Mgat5 overexpression upregulated β-1-6-GlcNAc branched N-glycosylation and following phosphorylation of epidermal growth factor receptor (EGFR) in hepatoma cells. EGFR tyrosine kinase inhibitors AG1478 and Iressa treatment declined anchorage-independent growth and anoikis resistance, which could be rescued by constitutive active mutant PAK1 T423E coexpression in Mgat5-overexpressed hepatoma cells. Conversely, knockdown of Mgat5 reduced EGFR/PAK1-dependent anoikis resistance, which could be reversed by PAK1 T423E. These results identified Mgat5-mediated β-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells, implicating that molecular targeted therapeutics against Mgat5/EGFR/PAK1 might open a new avenue for personalized medicine in advanced-stage HCC patients."}