PT - JOURNAL ARTICLE AU - Rui Lin AU - Xunxia Bao AU - Hui Wang AU - Sibo Zhu AU - Zhongyan Liu AU - Quanning Chen AU - Kaixing Ai AU - Baomin Shi TI - TRPM2 promotes pancreatic cancer by PKC/MAPK pathway AID - 10.1101/2020.11.09.373035 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.11.09.373035 4099 - http://biorxiv.org/content/early/2020/11/09/2020.11.09.373035.short 4100 - http://biorxiv.org/content/early/2020/11/09/2020.11.09.373035.full AB - Background The mechanism of pancreatic cancer(PA) is not fully understanded. In our last report, TRPM2 plays a promising role in pancreatic cancer. However, the mechanism of TRPM2 is still unknown in this dismal disease. This study was designed to investigate the role and mechanism of TRPM2 in pancreatic cancer.Methods TRPM2 overexpressed and siRNA plasmid were created and transfected with pancreatic cancer cell line(BxPC-3) to construct the cell model. We employed CCK-8, Transwell, scratch wound, and nude mice tumor bearing model to investigate the role of TRPM2 in pancreatic cancer. Besides, we collected the clinical data, tumor tissue sample(TT) and para-tumor sample(TP) from the pancreatic cancer patients treated in our hospital. We analyzed the mechanism of TRPM2 in pancreatic cancer by transcriptome analysis, Westernblot, and PCR.Results Overexpressed TRPM2 could promote pancreatic cancer in proliferation, migration, and invasion ability in no matter the cell model or nude mice tumor bearing model. TRPM2 level is highly negative correlated to the overall survival and progression-free survival time in PA patients, however, it is significantly increased in PA tissue as the tumor stage increases. The transcriptome analysis, GSEA analysis, Westernblot, and PCR results indicates TRPM2 is highly correlated with PKC/MAPK pathways.Conclusion TRPM2 could directly activate PKCα by calcium or indirectly activate PKCε and PKCδ by increased DAG in PC, which promote PC by downstream MAPK/MEK pathway activation.Competing Interest StatementThe authors have declared no competing interest.