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Plexin B1 suppresses c-Met in melanoma: a role for plexin B1 as a tumor-suppressor protein through regulation of c-Met.


ABSTRACT: Melanoma arises through complex genetic and epigenetic changes, resulting in uncontrolled proliferation, invasion, and metastatic disease. Semaphorins regulate axon guidance through interaction with their receptors, plexins and neuropilins. Plexin B1, the semaphorin 4D receptor, activates oncogenic receptors c-Met and ErbB-2 in several cell types, suggesting it promotes tumor growth through stimulation of these receptors. A study by Argast et al. has shown that plexin B1 is a tumor-suppressor protein for melanoma metastasis in a mouse model. In this report, we show that plexin B1 is lost in metastatic and deeply invasive melanoma in patient samples in vivo. Unexpectedly, introduction of plexin B1 into human melanoma cell lines suppressed, rather than activated, the oncogenic receptor, c-Met, by its ligand hepatocyte growth factor (HGF). Plexin B1 also activated Akt in melanoma. Plexin B1 significantly abrogated cell migration in response to HGF but rendered cells resistant to apoptosis by cisplatin. Plexin B1 is predicted to function as a classic tumor-suppressor protein in melanoma, in part through suppression of c-Met signaling and c-Met-dependent migration. However, because plexin B1 activates Akt, a multifunctional protein involved in tumor progression in several cancers, plexin B1 may function as a tumor promoter in melanomas not driven by c-Met activation.

SUBMITTER: Stevens L 

PROVIDER: S-EPMC3657133 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Plexin B1 suppresses c-Met in melanoma: a role for plexin B1 as a tumor-suppressor protein through regulation of c-Met.

Stevens Laurel L   McClelland Lindy L   Fricke Alex A   Williamson Magali M   Kuo Ihsin I   Scott Glynis G  

The Journal of investigative dermatology 20100218 6


Melanoma arises through complex genetic and epigenetic changes, resulting in uncontrolled proliferation, invasion, and metastatic disease. Semaphorins regulate axon guidance through interaction with their receptors, plexins and neuropilins. Plexin B1, the semaphorin 4D receptor, activates oncogenic receptors c-Met and ErbB-2 in several cell types, suggesting it promotes tumor growth through stimulation of these receptors. A study by Argast et al. has shown that plexin B1 is a tumor-suppressor pr  ...[more]

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