| Literature DB >> 33850109 |
Yang Pu1, Ya Song2,3, Mengdi Zhang2, Caifeng Long2, Jie Li2, Yanan Wang2, Yinzhe Xu4, Fei Pan4, Na Zhao2, Xinyu Zhang2, Yanan Xu5, Jianxin Cui4, Hongying Wang6, Yan Li7, Yong Zhao5, Di Jin8, Hongbing Zhang9.
Abstract
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 (GOLM1, also referred to as GP73) suppresses colorectal tumorigenesis via maintenance of intestinal epithelial barrier. GOLM1 deficiency in mice conferred susceptibility to mucosal inflammation and colitis-induced epithelial damage, which consequently promoted colon cancer. Mechanistically, depletion of GOLM1 in intestinal epithelial cells (IECs) 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 GOLM1-deficient mice. Therefore, GOLM1 maintains IEC homeostasis and protects against colitis and colon tumorigenesis by modulating the equilibrium of Notch signaling pathway.Entities:
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Year: 2021 PMID： 33850109 PMCID： PMC8044123 DOI： 10.1038/s41392-021-00535-1
Source DB: PubMed Journal: Signal Transduct Target Ther ISSN： 2059-3635