Positive expression of E-cadherin suppresses cell adhesion to fibronectin via reduction of alpha5beta1 integrin in human breast carcinoma cells.
E-cadherin mainly mediated the epithelial cell-cell adhesion, and integrin signaling can modulate the signaling pathway of E-cadherin in the different levels. Up to now, however, it is still unclear that whether E-cadherin could interfere with cell-matrix interaction, a typical adhesion through integrins. In this study we investigated the effects of E-cadherin on cell-matrix adhesion and alpha5beta1 integrin expression in human breast carcinoma cells. It was found that either mRNA or protein level of alpha5 and beta1 subunits of integrin decreased in E-cad-231 compared with Mock-231. Furthermore, the promoter activity of alpha5 gene was inhibited in E-cad-231 compared with Mock-231. Consistently, phosphorylated focal adhesion kinase, a closer key downstream protein kinase of integrin signaling, were also down-regulated in E-cad-231. Furthermore, distribution of beta-catenin was observed and data showed beta-catenin was accumulated in the nucleus in Mock-231, while disappeared from the nucleus and mainly accumulated near the cell surface membrane in E-cad-231. LiCl, a molecule that can inhibit the GSK-3beta activity and down-regulate beta-catenin degradation, could inversely stimulate expression of alpha5 and beta1 integrin. Taken together, these results indicated that positive expression of E-cadherin inhibits the cell adhesion to extracellular matrix mediated by alpha5beta1 integrin signaling.
Wu
Heng
H
Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Liang
Yu-Long
YL
Li
Zengxia
Z
Jin
Jiawei
J
Zhang
Wen
W
Duan
Lingling
L
Zha
Xiliang
X
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D012333:RNA, Messenger; D051176:beta Catenin; D014443:Tyrosine