DSC2 suppresses the growth of gastric cancer through the inhibition of nuclear translocation of ?-catenin and PTEN/PI3K/AKT signaling pathway

Background: Globally, gastric cancer (GC) is still a major leading cause of cancer-associated deaths. Downregulated desmocollin2 (DSC2) is considered to be closely related to tumor progression. However, the underlying mechanisms of DSC2 in GC progression require further exploration.Method: We initially constructed different GC cells based on DSC2 contents, established the mouse tumor xenografts, and subsequently performed clonal formation, MTT, Caspase-3 activity, and sperm DNA fragmentation assays to detect the functions of DSC2 in GC growth. Subsequently, we performed western blot, Co-IP, and immunofluorescence assays to investigate the underlying mechanisms through pretreatment with PI3K inhibitor, LY294002, and its activator, recombinant human insulin-like growth factor I (IGF1).Result: DSC2 could significantly inhibit the viability of GC cells at both in vitro and in vivo levels. The underlying mechanism may be that DSC2 binds the ?-catenin to decrease its nuclear level, thereby downregulating the anti-apoptotic factor BCL-2 expression and upregulating the pro-apoptotic factor P53 expression, which adjusts the PTEN/PI3K/AKT signaling pathway to promote the cancer cell apoptosis. Conclusions: Our finding suggests that DSC2 might be a potential therapeutic target for the treatment of cancers, most especially GC.