Skip to Main content Skip to Navigation
Journal articles

Up-regulation of MET Expression by α-Melanocyte-stimulating Hormone and MITF Allows Hepatocyte Growth Factor to Protect Melanocytes and Melanoma Cells from Apoptosis

Abstract : The MET proto-oncogene encodes for the hepatocyte growth factor (HGF) receptor, a plasma membrane tyrosine kinase that is involved in melanocyte growth and melanoma development. In mouse melanoma cells, Met expression is increased by alphaMSH via the activation of the cAMP pathway. However, the mechanism by which cAMP regulates MET and the biological consequences of this increase were not known. In the present report, we show that alphaMSH regulates MET expression in both human melanocytes and mouse melanoma cells through a transcriptional mechanism that requires MITF. Furthermore, the adenovirus driven expression of MITF is sufficient to increase MET in melanoma cells. Functional analysis of the MET promoter allows us to identify an E-box motif conserved in both human and mouse promoter that mediates the effect of MITF. Interestingly, up-regulation of MET expression by cAMP leads to an exacerbated HGF signaling and allows HGF to protect melanocytes and melanoma cells from apoptosis. Thus, physiological stimuli or pathological events that would induce MITF expression may lead to increased MET expression thereby favoring melanoma survival. These observations strengthen the roles of MITF and MET in melanoma development.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-02530853
Contributor : Bertolotto-Ballotti Bertolotto-Ballotti <>
Submitted on : Friday, April 3, 2020 - 11:33:28 AM
Last modification on : Wednesday, October 14, 2020 - 4:23:32 AM

Links full text

Identifiers

Collections

Citation

Laurent Beuret, Enrica Flori, Christophe Denoyelle, Karine Bille, Roser Buscà, et al.. Up-regulation of MET Expression by α-Melanocyte-stimulating Hormone and MITF Allows Hepatocyte Growth Factor to Protect Melanocytes and Melanoma Cells from Apoptosis. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2007, 282 (19), pp.14140-14147. ⟨10.1074/jbc.M611563200⟩. ⟨inserm-02530853⟩

Share

Metrics

Record views

27