GOLM1 restricts colitis and colon tumorigenesis by ensuring Notch signaling equilibrium in intestinal homeostasis

Intestinal epithelium serves as the first barrier against the infections and injuries that mediate colonic inflammation.Colorectal cancer is often accompanied with chronic inflammation.Differed from its well-known oncogenic role in many malignancies,we present here that Golgi membrane protein 1(G0LM1,also referred to as GP73)suppresses colorectal tumorigenesis via maintenance of intestinal epithelial barrier.G0LM1 deficiency in mice conferred susceptibility to mucosal inflammation and colitis-induced epithelial damage,which consequently promoted colon cancer.Mechanistically,depletion of G0LM1 in intestinal epithelial cells(lECs)led to aberrant Notch activation that interfered with IEC differentiation,maturation,and lineage commitment in mice.Pharmacological inhibition of Notch pathway alleviated epithelial lesions and restrained pro-tumorigenic inflammation in G0LM1-deficient mice.Therefore,G0LM1 maintains IEC homeostasis and protects against colitis and colon tumorigenesis by modulating the equilibrium of Notch signaling pathway.