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.

Details

Title
GOLM1 restricts colitis and colon tumorigenesis by ensuring Notch signaling equilibrium in intestinal homeostasis
Author
Yang, Pu 1 ; Song, Ya 2 ; Zhang, Mengdi 1 ; Long Caifeng 1 ; Li, Jie 1 ; Wang, Yanan 1 ; Xu Yinzhe 3 ; Pan Fei 3 ; Zhao, Na 1 ; Zhang, Xinyu 1 ; Xu, Yanan 4 ; Cui Jianxin 3 ; Wang, Hongying 5 ; Li, Yan 6 ; Zhao, Yong 4 ; Jin, Di 7 ; Zhang, Hongbing 1   VIAFID ORCID Logo 

1  Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, State Key Laboratory of Medical Molecular Biology, Department of Physiology, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
2  Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, State Key Laboratory of Medical Molecular Biology, Department of Physiology, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839); Dalian Medical University, Institute of Cancer Stem Cell, Dalian, China (GRID:grid.411971.b) (ISNI:0000 0000 9558 1426) 
3  Chinese PLA General Hospital, Beijing, China (GRID:grid.414252.4) (ISNI:0000 0004 1761 8894) 
4  State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (GRID:grid.458458.0) (ISNI:0000 0004 1792 6416) 
5  State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
6  College of Basic Medical Sciences, Shanghai Jiao Tong University, Department of Anatomy and Physiology, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
7  Dalian Medical University, Institute of Cancer Stem Cell, Dalian, China (GRID:grid.411971.b) (ISNI:0000 0000 9558 1426) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
ISSN
20959907
e-ISSN
20593635
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41392-021-00535-1
ProQuest document ID
2512157490
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.