PubMed:20857420 JSONTXT

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    sentences

    {"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":140},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":141,"end":227},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":228,"end":353},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":354,"end":647},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":648,"end":826},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":827,"end":961},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":962,"end":1051},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1052,"end":1233},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1234,"end":1326},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1327,"end":1443},"obj":"Sentence"},{"id":"TextSentencer_T11","span":{"begin":1444,"end":1532},"obj":"Sentence"},{"id":"TextSentencer_T12","span":{"begin":1533,"end":1666},"obj":"Sentence"},{"id":"TextSentencer_T13","span":{"begin":1667,"end":1841},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":140},"obj":"Sentence"},{"id":"T2","span":{"begin":141,"end":227},"obj":"Sentence"},{"id":"T3","span":{"begin":228,"end":353},"obj":"Sentence"},{"id":"T4","span":{"begin":354,"end":647},"obj":"Sentence"},{"id":"T5","span":{"begin":648,"end":826},"obj":"Sentence"},{"id":"T6","span":{"begin":827,"end":961},"obj":"Sentence"},{"id":"T7","span":{"begin":962,"end":1051},"obj":"Sentence"},{"id":"T8","span":{"begin":1052,"end":1233},"obj":"Sentence"},{"id":"T9","span":{"begin":1234,"end":1326},"obj":"Sentence"},{"id":"T10","span":{"begin":1327,"end":1443},"obj":"Sentence"},{"id":"T11","span":{"begin":1444,"end":1532},"obj":"Sentence"},{"id":"T12","span":{"begin":1533,"end":1666},"obj":"Sentence"},{"id":"T13","span":{"begin":1667,"end":1841},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    DisGeNET

    {"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1723,"end":1729},"obj":"gene:3091"},{"id":"T1","span":{"begin":1798,"end":1818},"obj":"disease:C0005779"},{"id":"T2","span":{"begin":1723,"end":1729},"obj":"gene:3091"},{"id":"T3","span":{"begin":1823,"end":1829},"obj":"disease:C0006826"},{"id":"T4","span":{"begin":1723,"end":1729},"obj":"gene:3091"},{"id":"T5","span":{"begin":1823,"end":1829},"obj":"disease:C1306459"},{"id":"T6","span":{"begin":1723,"end":1729},"obj":"gene:3091"},{"id":"T7","span":{"begin":1830,"end":1840},"obj":"disease:C0027627"},{"id":"T8","span":{"begin":1723,"end":1729},"obj":"gene:3091"},{"id":"T9","span":{"begin":1830,"end":1840},"obj":"disease:C2939420"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    PubmedHPO

    {"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":141,"end":161},"obj":"HP_0002625"},{"id":"T2","span":{"begin":187,"end":193},"obj":"HP_0002664"},{"id":"T3","span":{"begin":336,"end":341},"obj":"HP_0002664"},{"id":"T4","span":{"begin":553,"end":559},"obj":"HP_0002664"},{"id":"T5","span":{"begin":1034,"end":1039},"obj":"HP_0002664"},{"id":"T6","span":{"begin":1309,"end":1314},"obj":"HP_0002664"},{"id":"T7","span":{"begin":1738,"end":1743},"obj":"HP_0002664"},{"id":"T8","span":{"begin":1798,"end":1818},"obj":"HP_0001928"},{"id":"T9","span":{"begin":1823,"end":1829},"obj":"HP_0002664"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    Allie

    {"project":"Allie","denotations":[{"id":"SS1_20857420_2_0","span":{"begin":275,"end":302},"obj":"expanded"},{"id":"SS2_20857420_2_0","span":{"begin":304,"end":307},"obj":"abbr"},{"id":"SS1_20857420_3_0","span":{"begin":413,"end":431},"obj":"expanded"},{"id":"SS2_20857420_3_0","span":{"begin":433,"end":435},"obj":"abbr"},{"id":"SS1_20857420_6_0","span":{"begin":981,"end":1014},"obj":"expanded"},{"id":"SS2_20857420_6_0","span":{"begin":1016,"end":1019},"obj":"abbr"}],"relations":[{"id":"AE1_20857420_2_0","pred":"abbreviatedTo","subj":"SS1_20857420_2_0","obj":"SS2_20857420_2_0"},{"id":"AE1_20857420_3_0","pred":"abbreviatedTo","subj":"SS1_20857420_3_0","obj":"SS2_20857420_3_0"},{"id":"AE1_20857420_6_0","pred":"abbreviatedTo","subj":"SS1_20857420_6_0","obj":"SS2_20857420_6_0"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    DisGeNET5_gene_disease

    {"project":"DisGeNET5_gene_disease","denotations":[{"id":"20857420-0#63#90#gene3091","span":{"begin":63,"end":90},"obj":"gene3091"},{"id":"20857420-0#116#133#diseaseC0009402","span":{"begin":116,"end":133},"obj":"diseaseC0009402"},{"id":"20857420-0#116#133#diseaseC1527249","span":{"begin":116,"end":133},"obj":"diseaseC1527249"},{"id":"20857420-12#56#62#gene3091","span":{"begin":1723,"end":1729},"obj":"gene3091"},{"id":"20857420-12#163#173#diseaseC0027627","span":{"begin":1830,"end":1840},"obj":"diseaseC0027627"},{"id":"20857420-12#131#151#diseaseC0005779","span":{"begin":1798,"end":1818},"obj":"diseaseC0005779"},{"id":"20857420-2#87#92#gene9002","span":{"begin":315,"end":320},"obj":"gene9002"},{"id":"20857420-2#87#92#gene5074","span":{"begin":315,"end":320},"obj":"gene5074"},{"id":"20857420-2#87#92#gene347745","span":{"begin":315,"end":320},"obj":"gene347745"},{"id":"20857420-2#108#124#diseaseC0027627","span":{"begin":336,"end":352},"obj":"diseaseC0027627"},{"id":"20857420-3#53#58#gene2149","span":{"begin":407,"end":412},"obj":"gene2149"},{"id":"20857420-3#53#58#gene2011","span":{"begin":407,"end":412},"obj":"gene2011"},{"id":"20857420-3#53#58#gene8856","span":{"begin":407,"end":412},"obj":"gene8856"},{"id":"20857420-3#53#58#gene145624","span":{"begin":407,"end":412},"obj":"gene145624"},{"id":"20857420-3#53#58#gene79581","span":{"begin":407,"end":412},"obj":"gene79581"},{"id":"20857420-3#188#205#diseaseC0009402","span":{"begin":542,"end":559},"obj":"diseaseC0009402"},{"id":"20857420-3#188#205#diseaseC1527249","span":{"begin":542,"end":559},"obj":"diseaseC1527249"},{"id":"20857420-3#188#205#diseaseC0009402","span":{"begin":542,"end":559},"obj":"diseaseC0009402"},{"id":"20857420-3#188#205#diseaseC1527249","span":{"begin":542,"end":559},"obj":"diseaseC1527249"},{"id":"20857420-3#188#205#diseaseC0009402","span":{"begin":542,"end":559},"obj":"diseaseC0009402"},{"id":"20857420-3#188#205#diseaseC1527249","span":{"begin":542,"end":559},"obj":"diseaseC1527249"},{"id":"20857420-3#188#205#diseaseC0009402","span":{"begin":542,"end":559},"obj":"diseaseC0009402"},{"id":"20857420-3#188#205#diseaseC1527249","span":{"begin":542,"end":559},"obj":"diseaseC1527249"},{"id":"20857420-3#188#205#diseaseC0009402","span":{"begin":542,"end":559},"obj":"diseaseC0009402"},{"id":"20857420-3#188#205#diseaseC1527249","span":{"begin":542,"end":559},"obj":"diseaseC1527249"}],"relations":[{"id":"63#90#gene3091116#133#diseaseC0009402","pred":"associated_with","subj":"20857420-0#63#90#gene3091","obj":"20857420-0#116#133#diseaseC0009402"},{"id":"63#90#gene3091116#133#diseaseC1527249","pred":"associated_with","subj":"20857420-0#63#90#gene3091","obj":"20857420-0#116#133#diseaseC1527249"},{"id":"56#62#gene3091163#173#diseaseC0027627","pred":"associated_with","subj":"20857420-12#56#62#gene3091","obj":"20857420-12#163#173#diseaseC0027627"},{"id":"56#62#gene3091131#151#diseaseC0005779","pred":"associated_with","subj":"20857420-12#56#62#gene3091","obj":"20857420-12#131#151#diseaseC0005779"},{"id":"87#92#gene9002108#124#diseaseC0027627","pred":"associated_with","subj":"20857420-2#87#92#gene9002","obj":"20857420-2#108#124#diseaseC0027627"},{"id":"87#92#gene5074108#124#diseaseC0027627","pred":"associated_with","subj":"20857420-2#87#92#gene5074","obj":"20857420-2#108#124#diseaseC0027627"},{"id":"87#92#gene347745108#124#diseaseC0027627","pred":"associated_with","subj":"20857420-2#87#92#gene347745","obj":"20857420-2#108#124#diseaseC0027627"},{"id":"53#58#gene2149188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2149188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2149188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2149188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2149188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2149188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2149188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2149188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2149188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2149188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2149","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2011188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2011188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2011188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2011188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2011188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2011188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2011188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2011188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene2011188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene2011188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene2011","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene8856188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene8856188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene8856188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene8856188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene8856188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene8856188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene8856188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene8856188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene8856188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene8856188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene8856","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene145624188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene145624188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene145624188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene145624188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene145624188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene145624188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene145624188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene145624188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene145624188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene145624188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene145624","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene79581188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene79581188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene79581188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene79581188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene79581188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene79581188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene79581188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene79581188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC1527249"},{"id":"53#58#gene79581188#205#diseaseC0009402","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC0009402"},{"id":"53#58#gene79581188#205#diseaseC1527249","pred":"associated_with","subj":"20857420-3#53#58#gene79581","obj":"20857420-3#188#205#diseaseC1527249"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    DisGeNet-2017-sample

    {"project":"DisGeNet-2017-sample","denotations":[{"id":"T2330","span":{"begin":63,"end":90},"obj":"gene:3091"},{"id":"T2331","span":{"begin":116,"end":133},"obj":"disease:C0009402"},{"id":"T2332","span":{"begin":315,"end":320},"obj":"gene:9002"},{"id":"T2333","span":{"begin":336,"end":352},"obj":"disease:C0027627"},{"id":"T2334","span":{"begin":407,"end":412},"obj":"gene:2149"},{"id":"T2335","span":{"begin":542,"end":559},"obj":"disease:C0009402"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T2330","obj":"T2331"},{"id":"R2","pred":"associated_with","subj":"T2330","obj":"T2331"},{"id":"R3","pred":"associated_with","subj":"T2332","obj":"T2333"},{"id":"R4","pred":"associated_with","subj":"T2332","obj":"T2333"},{"id":"R5","pred":"associated_with","subj":"T2332","obj":"T2333"},{"id":"R6","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R7","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R8","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R9","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R10","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R11","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R12","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R13","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R14","pred":"associated_with","subj":"T2334","obj":"T2335"},{"id":"R15","pred":"associated_with","subj":"T2334","obj":"T2335"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    UBERON-AE

    {"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":146,"end":150},"obj":"http://purl.obolibrary.org/obo/UBERON_0001638"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":992,"end":1003},"obj":"http://purl.obolibrary.org/obo/UBERON_0003104"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}

    performance-test

    {"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":141,"end":150},"obj":"http://purl.obolibrary.org/obo/UBERON_0035552"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":146,"end":150},"obj":"http://purl.obolibrary.org/obo/UBERON_0001638"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":992,"end":1003},"obj":"http://purl.obolibrary.org/obo/UBERON_0003104"}],"text":"Thrombin induces expression of twist and cell motility via the hypoxia-inducible factor-1α translational pathway in colorectal cancer cells.\nDeep vein thrombosis associated with advanced cancer is known as Trousseau's syndrome. We hypothesized that thrombin, an activator of protease-activated receptor (PAR)-1 and PAR-4 contributes to tumor metastasis. In this study, we demonstrated that thrombin and the PAR-1 activating peptide (AP) SFLLRN, but not the PAR-4 AP GYPGKF, induced HIF-1α activities, protein expression, and cell motility in colorectal cancer cells, and these actions were significantly inhibited by the PAR-1 antagonist SCH79797. Moreover, thrombin-induced HIF-1α activity and cell motility were blocked by inhibiting important mediators of signaling transduction, including the ERK, PI3K, and mTOR pathways. These results showed that thrombin induced HIF-1α protein expression through PAR-1 and HIF-1α translational de novo protein synthesis. Twist can regulate epithelial-mesenchymal transition (EMT) and increase tumor metastasis. However, we observed that thrombin-induced HIF-1α increased Twist mRNA and its protein level was mediated by the modulation of PAR-1 activation and the HIF-1α translational pathway. In addition, Twist could increase N-cadherin but not E-cadherin to promote tumor metastasis. Overexpression of dominant-negative HIF-1α reversed thrombin-mediated Twist and Twist-induced N-cadherin expression. Moreover, siTwist inhibited Twist-induced N-cadherin and Thrombin-induced cell motility. In conclusion, our study showed that thrombin-induced HIF-1α upregulated Twist at the transcriptional level to enhance cell motility. These findings show that thrombin upregulates Twist via HIF-1α to make tumor cells malignant and also establish a link between the coagulation disorder and cancer metastasis."}