PubMed:11518717 JSONTXT

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":436,"end":439},"obj":"Glycan_Motif"},{"id":"T2","span":{"begin":515,"end":518},"obj":"Glycan_Motif"},{"id":"T3","span":{"begin":568,"end":571},"obj":"Glycan_Motif"},{"id":"T4","span":{"begin":630,"end":633},"obj":"Glycan_Motif"},{"id":"T5","span":{"begin":819,"end":822},"obj":"Glycan_Motif"},{"id":"T6","span":{"begin":924,"end":927},"obj":"Glycan_Motif"},{"id":"T7","span":{"begin":1167,"end":1170},"obj":"Glycan_Motif"},{"id":"T8","span":{"begin":1522,"end":1525},"obj":"Glycan_Motif"},{"id":"T9","span":{"begin":1633,"end":1636},"obj":"Glycan_Motif"},{"id":"T10","span":{"begin":1698,"end":1701},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A2","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A3","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A4","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A5","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A6","pred":"image","subj":"T6","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A7","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A8","pred":"image","subj":"T8","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A9","pred":"image","subj":"T9","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"},{"id":"A10","pred":"image","subj":"T10","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00063MO"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":120},"obj":"Sentence"},{"id":"T2","span":{"begin":121,"end":299},"obj":"Sentence"},{"id":"T3","span":{"begin":300,"end":441},"obj":"Sentence"},{"id":"T4","span":{"begin":442,"end":598},"obj":"Sentence"},{"id":"T5","span":{"begin":599,"end":720},"obj":"Sentence"},{"id":"T6","span":{"begin":721,"end":963},"obj":"Sentence"},{"id":"T7","span":{"begin":964,"end":1098},"obj":"Sentence"},{"id":"T8","span":{"begin":1099,"end":1194},"obj":"Sentence"},{"id":"T9","span":{"begin":1195,"end":1430},"obj":"Sentence"},{"id":"T10","span":{"begin":1431,"end":1672},"obj":"Sentence"},{"id":"T11","span":{"begin":1673,"end":1764},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":436,"end":439},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T2","span":{"begin":515,"end":518},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T3","span":{"begin":568,"end":571},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T4","span":{"begin":630,"end":633},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T5","span":{"begin":819,"end":822},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T6","span":{"begin":924,"end":927},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T7","span":{"begin":1167,"end":1170},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T8","span":{"begin":1522,"end":1525},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T9","span":{"begin":1633,"end":1636},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"},{"id":"T10","span":{"begin":1698,"end":1701},"obj":"https://glytoucan.org/Structures/Glycans/G00063MO"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"11518717-0#0#14#gene3480","span":{"begin":0,"end":14},"obj":"gene3480"},{"id":"11518717-0#51#64#diseaseC0006142","span":{"begin":51,"end":64},"obj":"diseaseC0006142"},{"id":"11518717-0#51#64#diseaseC0678222","span":{"begin":51,"end":64},"obj":"diseaseC0678222"},{"id":"11518717-1#62#68#gene3480","span":{"begin":183,"end":189},"obj":"gene3480"},{"id":"11518717-1#140#146#gene3480","span":{"begin":261,"end":267},"obj":"gene3480"},{"id":"11518717-1#150#166#diseaseC0027627","span":{"begin":271,"end":287},"obj":"diseaseC0027627"}],"relations":[{"id":"0#14#gene348051#64#diseaseC0006142","pred":"associated_with","subj":"11518717-0#0#14#gene3480","obj":"11518717-0#51#64#diseaseC0006142"},{"id":"0#14#gene348051#64#diseaseC0678222","pred":"associated_with","subj":"11518717-0#0#14#gene3480","obj":"11518717-0#51#64#diseaseC0678222"},{"id":"62#68#gene3480150#166#diseaseC0027627","pred":"associated_with","subj":"11518717-1#62#68#gene3480","obj":"11518717-1#150#166#diseaseC0027627"},{"id":"140#146#gene3480150#166#diseaseC0027627","pred":"associated_with","subj":"11518717-1#140#146#gene3480","obj":"11518717-1#150#166#diseaseC0027627"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"CoMAGC","denotations":[{"id":"T1","span":{"begin":456,"end":462},"obj":"Gene"},{"id":"E1","span":{"begin":463,"end":477},"obj":"Gene_expression"},{"id":"E2","span":{"begin":463,"end":477},"obj":"Positive_regulation"},{"id":"T2","span":{"begin":534,"end":547},"obj":"breast cancer"},{"id":"T3","span":{"begin":581,"end":591},"obj":"breast cancer"},{"id":"T4","span":{"begin":528,"end":533},"obj":"breast cancer"}],"relations":[{"id":"R1","pred":"themeOf","subj":"T1","obj":"E1"},{"id":"R2","pred":"themeOf","subj":"E1","obj":"E2"},{"id":"R3","pred":"CGE-increased","subj":"T1","obj":"T2"},{"id":"R4","pred":"CCS-unidentifiable","subj":"T1","obj":"T2"},{"id":"R5","pred":"PT-","subj":"T1","obj":"T2"},{"id":"R3","pred":"IGE-","subj":"T1","obj":"T2"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":144,"end":181},"obj":"gene:3480"},{"id":"T1","span":{"begin":214,"end":227},"obj":"disease:C0006142"},{"id":"T2","span":{"begin":144,"end":181},"obj":"gene:3480"},{"id":"T3","span":{"begin":214,"end":227},"obj":"disease:C0678222"},{"id":"T4","span":{"begin":183,"end":189},"obj":"gene:3480"},{"id":"T5","span":{"begin":214,"end":227},"obj":"disease:C0006142"},{"id":"T6","span":{"begin":183,"end":189},"obj":"gene:3480"},{"id":"T7","span":{"begin":214,"end":227},"obj":"disease:C0678222"},{"id":"T8","span":{"begin":183,"end":189},"obj":"gene:3480"},{"id":"T9","span":{"begin":271,"end":287},"obj":"disease:C0027627"},{"id":"T10","span":{"begin":183,"end":189},"obj":"gene:3480"},{"id":"T11","span":{"begin":271,"end":287},"obj":"disease:C2939419"},{"id":"T12","span":{"begin":261,"end":267},"obj":"gene:3480"},{"id":"T13","span":{"begin":271,"end":287},"obj":"disease:C0027627"},{"id":"T14","span":{"begin":261,"end":267},"obj":"gene:3480"},{"id":"T15","span":{"begin":271,"end":287},"obj":"disease:C2939419"}],"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"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"},{"id":"R8","pred":"associated_with","subj":"T14","obj":"T15"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":51,"end":64},"obj":"Disease"},{"id":"T2","span":{"begin":206,"end":227},"obj":"Disease"},{"id":"T3","span":{"begin":271,"end":276},"obj":"Disease"},{"id":"T4","span":{"begin":534,"end":547},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":51,"end":57},"obj":"Body_part"},{"id":"T2","span":{"begin":98,"end":106},"obj":"Body_part"},{"id":"T3","span":{"begin":214,"end":220},"obj":"Body_part"},{"id":"T4","span":{"begin":534,"end":540},"obj":"Body_part"},{"id":"T5","span":{"begin":937,"end":953},"obj":"Body_part"},{"id":"T6","span":{"begin":1653,"end":1671},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0007651"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/GO_0005923"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/GO_0015629"}],"text":"IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1.\nHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects."}