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Disruption of GRM 1‐mediated signalling using riluzole results in DNA damage in melanoma cells
Author(s) -
Wall Brian A.,
WangariTalbot Janet,
Shin Seung S.,
Schiff Devora,
Sierra Jairo,
Yu Lumeng J.,
Khan Atif,
Haffty Bruce,
Goydos James S.,
Chen Suzie
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12207
Subject(s) - riluzole , metabotropic glutamate receptor , glutamate receptor , metabotropic glutamate receptor 1 , microbiology and biotechnology , receptor , melanoma , in vivo , in vitro , chemistry , biology , cancer research , biochemistry , genetics
Summary Gain of function of the neuronal receptor, metabotropic glutamate receptor 1 ( G rm1), was sufficient to induce melanocytic transformation in vitro and spontaneous melanoma development in vivo when ectopically expressed in melanocytes. The human form of this receptor, GRM 1, has been shown to be ectopically expressed in a subset of human melanomas but not benign nevi or normal melanocytes, suggesting that misregulation of GRM 1 is involved in the pathogenesis of certain human melanomas. Sustained stimulation of G rm1 by the ligand, glutamate, is required for the maintenance of transformed phenotypes in vitro and tumorigenicity in vivo. In this study, we investigate the mechanism of an inhibitor of glutamate release, riluzole, on human melanoma cells that express metabotropic glutamate receptor 1 ( GRM 1). Various in vitro assays conducted show that inhibition of glutamate release in several human melanoma cell lines resulted in an increase of oxidative stress and DNA damage response markers.