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Our team has added to the knowledge of aberrant signaling in melanoma by discovering the expression of the G protein couple receptor, metabotropic glutamate receptor 1 in melanocytes was adequate to induce natural melanoma development in vivo with 100% penetrance. We also confirmed ectopic expression of GRM1 in a part of human melanoma cell Tipifarnib lines and biopsies. Thus far, we have reviewed over 175 human melanoma biopsies as well as 25 human melanoma cell lines and observed that 80% of the cell lines and over 600-800 of the human biopsies test positive for expression of the receptor at the level of both RNA and protein, suggesting that GRM1 could be involved with the pathogenesis of a significant subset of human melanomas. Our work has recently been confirmed by a report indicating that transgenic mice with conditional expression of GRM1 in melanocytes designed pigmented lesions at 29 weeks after service of the transgene with the incidence of subsequent melanoma being a century at 52 weeks. We've worked to solve Endosymbiotic theory the causes and effects of GRM1 signaling in this disease in addition to design therapeutic interventions that target GRM1 signaling. Earlier, we described in vitro and in vivo pre-clinical findings using human melanoma cell lines which are wild-type in B RAF and Deborah RAS or contain an N RASQ61R mutation. We demonstrated that MAPK signaling is critical in GRM1 mediated oncogenesis and have revealed that activation of the receptor using known GRM1 agonists in an up-regulation of the form of ERK. In addition, the vast majority of GRM1 expressing human melanoma cell lines tested shown increased degrees of extracellular glutamate which promotes growth by activation of the glutamate autocrine loop. Reduction of GRM1 signaling by either GRM1 antagonists or even a reduction Gemcitabine in the degrees of GRM1 ligand, glutamate, having a glutamate release inhibitor Riluzole, resulted in reduced cell growth in vitro and tumorigenesis in vivo. The US Food and Drug Administration authorized Riluzole, is an associate of the benzothiazole class of compounds and acts as an inhibitor of glutamate release for the therapy of amyotrophic lateral sclerosis. The power of Riluzole to block the release of the ligand for GRM1 allows it to act functionally like a putative antagonist and restrict intracellular events that follow stimulation of this receptor. Using a reduced toxicity account, Riluzole was deemed an excellent compound to make use of in preliminary studies on the effects of glutamate signaling inhibition on cancer cells. Thus far, the reported modes of activities of Riluzole in people are inhibition of glutamate release, inactivation of voltage dependent Na channels, and interference with G protein dependent signaling.