A novel methylated cation channel TRPM4 inhibited colorectal cancer metastasis through Ca²⁺/Calpain-mediated proteolysis of FAK and suppression of PI3K/Akt/mTOR signaling pathway.

ABSTRACT: Colorectal cancer (CRC) is an aggressive malignancy with poor prognosis. It is imperative to elucidate the potential molecular mechanisms that regulate CRC cell aggressiveness. In present study, the transient receptor potential melastatin 4 (TRPM4), a calcium-activated nonselective cation channel, is downregulated in CRC as a novel methylated tumor suppressor gene (TSG). The reduced mRNA level of TRPM4 is due to the epigenetic methylation of its promoter CpG island (CGI). Moreover, ectopic expression of TRPM4 inhibited tumor growth and metastasis both in vitro and in vivo. Our experiments also demonstrate that TRPM4 restructures the CRC cytoskeleton and activates the Ca²⁺-mediated calpain pathway through enhancing calcium influx. The western blot analysis shows that the expressi

SUBMITTER: Wang C 

PROVIDER: S-EPMC9461655 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature