The role of novel cytoskeleton septin 9 in junctional regulation and colorectal cancer development

Colorectal cancer (CRC) accounts for over 130,000 new cases and 50,000 deaths annually in the U.S., with complex etiological and development mechanisms. Septin 9 (SEPT9) is a member of the novel cytoskeleton septins and has been shown to correlate with CRC development and diagnosis. The mechanisms of SEPT9-conducted CRC regulation are elucidative. We hypothesized that SEPT9 regulates CRC by maintaining intestinal epithelium integrity. The intestinal epithelium-specific knockout mice (cKO) and the control mice (Ctrl) were employed for the DSS/AOM-induced CRC challenge. SPET9-KO The SEPT9 knockout changed the morphology of epithelial cells and caused an increase in intestinal permeability. SEPT9-KO in polarized cell line cause a similar permeability increase, with a decreased claudin-3 expression and non-muscle myosin IIC dysregulation. The CRC treatment caused higher mortality and tumor load in cKO mice. Our results demonstrated that SEPT9 regulates CRC development by maintaining intestinal epithelial integrity.