TRPM8 Ion Channels as Potential Cancer Biomarker and Target in Pancreatic Cancer

Abstract

This article provides a review and discussion of the transient receptor potential melastatin-subfamily member 8 (TRPM8) ion channel as a potential biomarker and target in cancer. TRPM8 is a Ca(2+)-permeable channel that plays a major physiological role in cellular sensation and transduction of cold temperature. TRPM8 is aberrantly expressed in a variety of solid tumors including pancreatic cancer. In pancreatic adenocarcinoma cell lines and tissues, TRPM8 is overexpressed as compared to normal pancreatic ductal epithelia. Analysis of anti-TRPM8 immunoreactivity in pancreatic adenocarcinoma indicates positive correlation of TRPM8 expression with tumor size and stages. The biological roles of TRPM8 in pancreatic cancer cells have been revealed from studies using RNA interference-mediated silencing of TRPM8. The experimental data show that TRPM8 channels are required for sustaining proliferation and cell cycle progression, preventing replicative senescence, and promoting cell invasion. Evidence to date implicates a contributory role of TRPM8 channels in the pathogenesis of pancreatic neoplasms and other tumors. Research focus on the mechanisms that underlie TRPM8-mediated roles in tumor growth and metastasis may help establish a novel link of physicochemical changes with pancreatic carcinogenesis. Translational and clinical investigation to exploit TRPM8 as a molecular biomarker and therapeutic target is expected to make a positive impact on precision medicine in pancreatic cancer and other malignant diseases.

Keywords: Biomarker; Ion channel; Pancreatic cancer; Precision oncology; TRPM7; TRPM8; Target.