Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transformation of normal melanocytes, or melanocyte stem cells, to melanoma, is a complex process involving multiple mechanisms. Loss of tumor suppressor proteins, which function as brakes on cell growth, migration, or cell survival, was recognized early on as an important mechanism for initiation and progression of melanoma. Semaphorins and their cognate receptors, Plexins and neuropilins, are involved in neuronal pathfinding, immune function, and tumor progression through effects on blood vessel growth and cell migration. Semaphorin 7A (Sema7A) is a membrane-linked semaphorin that is expressed by human keratinocytes, and we have shown that Sema7A binds to human melanocytes through beta1-integrins and the Plexin C1 receptor. Functional studies showed that Sema7A stimulates cytoskeletal reorganization in human melanocytes, resulting in adhesion and dendrite formation. Downstream targets of Plexin C1 signaling in human melanocytes include cofilin and LIM kinase II, both of which are critical mediators of cell adhesion and migration. In this report, we analyzed the expression of Plexin C1 using immunohistochemistry on sections of primary and matched metastatic lesions from 19 subjects and in a large melanoma tumor microarray. Our data show a significant loss of Plexin C1 in metastatic melanoma compared with primary melanoma, suggesting the possibility that the Plexin C1 receptor is a tumor suppressor protein for melanoma.
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PMID:The semaphorin 7A receptor Plexin C1 is lost during melanoma metastasis. 1931 6

Metastatic melanoma is a life-threatening disease for which no effective treatment is currently available. In melanoma cells, Rho overexpression promotes invasion and metastasis. However, the effect of statins on spontaneous metastasis and tumor growth remains unclear. In the present study, we investigated the mechanism of statin-mediated tumor growth and metastasis inhibition in an in vivo model. We found that statins significantly inhibited spontaneous metastasis and tumor growth. Statins inhibited the mRNA expression and enzymatic activities of matrix metalloproteinases (MMPs) in vivo and also suppressed the mRNA and protein expression of very late antigens (VLAs). Moreover, statins inhibited the prenylation of Rho as well as the phosphorylation of LIM kinase, serum response factor (SRF), and c-Fos downstream of the Rho signaling pathway. In addition, statins enhanced p53, p21, and p27 expression and reduced phosphorylation of cyclin-dependent kinase and expression of cyclin D1 and E2. These results indicate that statins suppress Rho signaling pathways, thereby inhibiting tumor metastasis and growth. Furthermore, statins markedly improved the survival rate in a metastasis model, suggesting that statins have potential clinical applications for the treatment of metastatic cancers.
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PMID:Statins improve survival by inhibiting spontaneous metastasis and tumor growth in a mouse melanoma model. 2669 69