Lvania State University, Hershey, PA 17033, USA; [email protected]; Tel.: +1-717-531-0003 (ext. 289532); Fax: +1-717-531-Abstract: The purpose of this short article is always to supply a critical review in the transient receptor prospective melastatin-subfamily member 8 (TRPM8) in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca2` homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating proof has demonstrated that TRPM8 is aberrantly expressed inside a selection of malignant strong tumors. Clinicopathological evaluation has shown that over-expression of TRPM8 correlates with tumor progression. Experimental information have revealed critical roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which seem to become dependent on the cancer type. Recent reports have begun to Lanicemine Description reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor 556-03-6 Epigenetic Reader Domain growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the effect of thermal and chemical stimuli around the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will aid exploit these ion channels as molecular biomarkers and therapeutic targets for establishing precision cancer medicine. Keywords and phrases: calcium; cancer; cell cycle; ion channels; invasion; proliferation; senescence; survival; TRPM1. Introduction This article focuses on the transient receptor potential melastatin-subfamily member 8 (TRPM8) ion channel in cancers, with an emphasis on its roles in proliferation, survival, and invasion. As a regulator of Ca2` homeostasis, the TRPM8 ion channel functions as a cellular sensor and transducer of cold temperature. Even though typical expression is tissue-selective, TRPM8 is aberrantly expressed inside a variety of malignant tumors. Experimental information implicate that TRPM8 channels play vital roles in cancer cells proliferation, survival, migration, invasion, and neurosecretion. Quite a few in vivo studies have implicated the contributory roles of TRPM8 in cancer development and metastasis. The etiological function of TRPM8 as a cold sensor in malignant neoplasia is primarily unknown. Study efforts to identify the mechanistic roles of TRPM8 in cancer are anticipated to shed new light on how the physical and chemical alterations inside the atmosphere impact on carcinogenesis. TRPM8 is usually a member in the TRP superfamily of ion channels that ordinarily function in diverse physiological responses [1]. The human TRPM8 gene in chromosome two encodes a non-selective, voltage-gated, and Ca2` permeable ion channel [2,3]. TRPM8 protein consists of 1104 amino acid residues, having a molecular mass of 128 kDa. In human adult tissues, TRPM8 mRNA is highlyCancers 2015, 7, 2134146; doi:10.3390/cancers7040882 www.mdpi.com/journal/cancersCancers 2015, 7, 2134expressed in the prostate gland [4]. It’s also detected in the liver, dorsal root ganglion, and trigeminal ganglion neurons [5]. Under physiological situations, TRPM8 ion channels are essential for sensation of coolness [6] and serum homeostasis of insulin [9]. Accumulating evidence implicates that TRPM8 is involved in diverse human disorders, particularly cancer. Within this write-up, I provide an overview in the TRPM8 ion channel relating to its structural features Cancers 2015, 7, web page age and physiological functions. The expression and roles of TRPM8 channels in vari.