Abstract
Esophageal cancer is seen with increasing incidence, but the underlying mechanism of esophageal cancer is still unknown. Transient receptor potential melastatin (TRPM) is non-selective cation channels. It has been verified that TRPM channels play crucial roles in development and progression of multiple tumors. Increasing studies have shown that TRPM8, a member of TRPM channels, promotes growth of tumors. However, it is still unclear whether TRPM8 has biological effect on esophageal cancer. In the current work, we found that TRPM8 was overexpressed in esophageal cancer samples and cell lines. Further investigation revealed that TRPM8 promoted proliferation of esophageal cancer cells. Next, the co-incubation assay including EC109 cells and CD8+ T cells revealed that TRPM8 overexpression and TRPM8 agonist reduced the cytotoxic effect of CD8+ T cell on esophageal cancer cells. Finally, we explored the mechanism and found that calcineurin-nuclear factor of activated T cells 3 (NFATc3) pathway contributed to the expression of programmed death ligand 1 (PD-L1) induced by TRPM8 overexpression and TRPM8 agonist, which might lead to immune evasion of esophageal cancer cells. These findings uncovered the crucial role of TRPM8 in the pathogenesis of esophageal cancer.
Highlights
Esophageal cancer is one of the malignancies, which ranks fourth in the incidence and mortality of malignant tumors in digestive system all over the world [1]
We found TRPM8 was up-regulated in esophageal cancer
We proved that TRPM8 regulated programmed death ligand 1 (PD-L1) expression by calcineurin-nuclear factor of activated T cells 3 (NFATc3) pathway in esophageal cancer cells
Summary
Esophageal cancer is one of the malignancies, which ranks fourth in the incidence and mortality of malignant tumors in digestive system all over the world [1]. In China, esophageal cancer ranks second in the incidence and third in the mortality of malignant tumors in digestive system [2]. A variety of therapies are applied, surgery is still thought to be the primary treatment for esophageal cancer [3,4]. To clarify the underlying mechanisms will contribute to the development of novel drugs for esophageal cancer. It has been reported that TRP superfamily consists of six subfamily members, among which TRP melastatin (TRPM) is investigated thoroughly and extensively compared with other TRP subfamilies in the development and progression of tumors [6,7]
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