Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Met and Ron tyrosine kinases are members of the Scatter Factor Receptor family. Met is the receptor for hepatocyte growth factor while Ron is that for macrophage stimulating protein. On ligand stimulation, activation of these receptors induces 'invasive growth', a complex biological response involved in tissue morphogenesis and, when deregulated, in tumor progression and metastasis. Scatter Factor Receptors share structural homology with Plexins, transmembrane receptors for Semaphorins, a family of ligands originally identified as axon guidance molecules. A physical and functional association between Met and Plexin B1, the prototype of class B Plexin subfamily, has been previously demonstrated. Here, we show that both Met and Ron receptors can interact with each of the three members of class B Plexins, even in the absence of their ligands and that Plexin B1 ligand, Sema 4D, can induce activation of Met and Ron receptors, promoting an invasive response. Furthermore, in some human neoplastic cell lines Plexin B1 is overexpressed, constitutively tyrosine phosphorylated, and associated with Scatter Factor Receptors. These data extend the crosstalk previously described between Met and Plexin B1 to the entire families of Scatter Factor Receptors and class B Plexins and show that interaction with multiple upstream activators can finely tune the invasive growth process both in physiological conditions and in tumor growth and metastatization.
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PMID:Interplay between scatter factor receptors and B plexins controls invasive growth. 1518 88

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.
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PMID:Plexin B1 suppresses c-Met in melanoma: a role for plexin B1 as a tumor-suppressor protein through regulation of c-Met. 2016 43