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HGF induces FAK activation and integrin‐mediated adhesion in MTLn3 breast carcinoma cells
Author(s) -
Beviglia Lucia,
Kramer Randall H.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991126)83:5<640::aid-ijc13>3.0.co;2-d
Subject(s) - focal adhesion , integrin , extracellular matrix , tyrosine phosphorylation , fibronectin , microbiology and biotechnology , ptk2 , hepatocyte growth factor , phosphorylation , motility , cell adhesion , receptor tyrosine kinase , cell adhesion molecule , tyrosine kinase , cancer research , laminin , tyrosine , adhesion , biology , signal transduction , chemistry , cell , receptor , protein kinase a , biochemistry , mitogen activated protein kinase kinase , organic chemistry
Expression of hepatocyte growth factor (HGF) and its tyrosine kinase receptor, c‐Met, is positively correlated with breast carcinoma progression. We found that in invasive and metastatic MTLn3 breast carcinoma cells, HGF stimulated both initial adhesion to and motility on the extracellular matrix (ECM) ligands laminin 1, type I collagen, and fibronectin. Next, analysis with function‐perturbing antibodies showed that adhesion to the different ECM proteins was mediated through specific β1 integrins. In MTLn3 cells, HGF induced rapid tyrosine phosphorylation and activation of both c‐Met and focal adhesion kinase (FAK). Cell anchorage and adhesion to the ECM substrates was required for HGF‐induced FAK activation, since HGF failed to trigger tyrosine phosphorylation of FAK in suspended cells. Our results provide evidence that the 2 signaling pathways, integrin/ECM and c‐Met/HGF, cooperate synergistically to induce FAK activation in an adhesion‐dependent manner, leading to enhanced cell adhesion and motility. Moreover, we found that a FRNK (the FAK‐related non‐kinase)‐like molecule is expressed in MTLn3 cells. Since FRNK acts as a competitive inhibitor of FAK function, our results suggest that a FRNK‐like protein could facilitate disassembly of focal adhesions and likely be responsible for the HGF‐induced scattering and motility of MTLn3 cells. Int. J. Cancer 83:640‐649, 1999. © 1999 Wiley‐Liss, Inc.