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Plexin B1 inhibits integrin‐dependent pp125 FAK and Rho activity in melanoma
Author(s) -
McClelland Lindy,
Chen YuLin,
Soong Joanne,
Kuo IHsin,
Scott Glynis
Publication year - 2011
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2010.00797.x
Subject(s) - plexin , semaphorin , integrin , microbiology and biotechnology , melanoma , cancer research , cell migration , hepatocyte growth factor , chemistry , receptor , biology , cell , biochemistry
Summary Semaphorins are secreted and membrane bound proteins that regulate axon guidance through receptors Plexins and neuropilins. Plexin B1, the Semaphorin 4D receptor, is a recently described tumor suppressor protein for melanoma. We recently showed that Plexin B1 abrogates activation of the oncogenic receptor, c‐Met, by its ligand, hepatocyte growth factor (HGF), in melanoma. We have now investigated the effect of Plexin B1 on integrin‐dependent pp125 FAK activation, and the small GTP‐binding protein Rho, in melanoma. Integrin receptors and Rho play critical roles in melanoma progression, through regulation of migration, proliferation and apoptosis. We engineered two human melanoma cell lines expressing Plexin B1 and analyzed integrin‐dependent migration, integrin‐dependent pp125 FAK activation, and Rho activity. Results show that Plexin B1 abrogates integrin‐dependent migration and activation of pp125 FAK . We also show that Rho activity is significantly reduced in cells expressing Plexin B1, and that Plexin B1 suppresses HGF‐dependent Rho activation.