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Metabotropic glutamate receptor 1 mediates melanocyte transformation via transactivation of insulin‐like growth factor 1 receptor
Author(s) -
Teh Jessica L. F.,
Shah Raj,
Shin SeungShick,
Wen Yu,
Mehnert Janice M.,
Goydos James,
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.12237
Subject(s) - cancer research , protein kinase b , receptor tyrosine kinase , growth factor receptor , biology , carcinogenesis , epidermal growth factor receptor , metabotropic glutamate receptor 1 , pi3k/akt/mtor pathway , in vivo , microbiology and biotechnology , chemistry , receptor , signal transduction , glutamate receptor , metabotropic glutamate receptor , biochemistry , genetics , gene
Summary Our laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (m G lu R 1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in m G lu R 1‐mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet‐R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both m G lu R 1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable m G lu R 1‐melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between m G lu R 1 and tyrosine kinase, insulin‐like growth factor 1 receptor (IGF‐1R).