Role of TRPM in melanocytes and melanoma.
Transient receptor potential (TRP) cation channel superfamily plays important roles in variety cellular processes including polymodal cellular sensing, cell adhesion, cell polarity, proliferation, differentiation and apoptosis. One of its subfamilies are TRPM channels. mRNA expression of its founding member, TRPM1 (melastatin), correlates with terminal melanocytic differentiation and loss of its expression has been identified as an important diagnostic and prognostic marker for primary cutaneous melanoma. Because TRPM1 gene codes two transcripts: TRPM1 channel protein in its exons and miR-211 in one of its introns, we propose a dual role for TRPM1 gene where the loss of TRPM1 channel protein is an excellent marker of melanoma aggressiveness, while the expression of miR-211 is linked to the tumor suppressor function of TRPM1. In addition, three other members of this subfamily, TRPM 2, 7 and 8 are implicated in the regulation of melanocytic behaviour. TRPM2 is capable of inducing melanoma apoptosis and necrosis. TRPM7 can be a protector and detoxifier in both melanocytes and melanoma cells. TRPM8 can mediate agonist-induced melanoma cell death. Therefore, we propose that TRPM1, TRPM2, TRPM7 and TRPM8 play crucial roles in melanocyte physiology and melanoma oncology and are excellent diagnostic markers and theraputic targets.
Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, USA.
Huazhang
H
Guo
John Andrew
JA
Carlson
Andrzej
A
Slominski
D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005091:Exons; D006801:Humans; D007438:Introns; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009336:Necrosis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism*
D014408:Biomarkers, Tumor; C549405:MIRN211 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; C121934:TRPM2 protein, human; C425966:TRPM8 protein, human; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human