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Targets of Signal Transduction Pathways in Melanoma
Author(s) -
Ahn Natalie
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a852-d
Subject(s) - focal adhesion , rhoa , microbiology and biotechnology , stress fiber , melanoma , signal transduction , ptk2 , cancer research , mapk/erk pathway , gtpase , biology , tyrosine phosphorylation , rac1 , cell adhesion , cell , protein kinase c , mitogen activated protein kinase kinase , biochemistry
Melanoma derives from epidermal melanocytes which develop to metastatic cancer through a multistage progression process. Our work examines signaling pathways that are aberrantly activated in melanoma in order to understand the mechanisms by which they contribute to this disease. We have found that Rho and Rac GTPase pathways are constitutively activated in melanoma cell lines in a stage‐specific manner, where activation of Rac occurs in early stages, and activation of Rho occurs in late, metastatic stages. Using proteomics profiling we identified a novel target of RhoA, named Mediator of Rho‐dependent Invasion (MRDI), which is selectively expressed in metastatic cells and promotes cell invasion. MRDI colocalizes at membrane ruffles with neuronal Wiskott‐Aldrich syndrome protein (N‐WASP) and is required for tyrosine phosphorylation of focal adhesion kinase. Although MRDI is not located in focal adhesion contacts, its expression leads to small focal adhesion size and reduced stress fiber formation, suggesting that it controls cell invasion by enhancing focal adhesion turnover. In addition, published studies have demonstrated activation of the B‐Raf/MKK/ERK pathway in melanoma tumors. We will discuss mechanisms that may enable B‐Raf to crossregulate Rho GTPase pathways in a manner contributing to cancer progression.