2. Academic Validation
  3. GOLM1 restricts colitis and colon tumorigenesis by ensuring Notch signaling equilibrium in intestinal homeostasis

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

  • Signal Transduct Target Ther. 2021 Apr 14;6(1):148. doi: 10.1038/s41392-021-00535-1.
Yang Pu  # 1,  Ya Song  # 2 3,  Mengdi Zhang 2,  Caifeng Long 2,  Jie Li 2,  Yanan Wang 2,  Yinzhe Xu 4,  Fei Pan 4,  Na Zhao 2,  Xinyu Zhang 2,  Yanan Xu 5,  Jianxin Cui 4,  Hongying Wang 6,  Yan Li 7,  Yong Zhao 5,  Di Jin 8,  Hongbing Zhang 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. puyang_py@163.com.
  • 2 State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
  • 3 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
  • 4 Chinese PLA General Hospital, Beijing, China.
  • 5 State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 6 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.
  • 7 Department of Anatomy and Physiology, College of Basic Medical Sciences, Shanghai Jiao Tong University, Shanghai, China.
  • 8 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China. jindi0801@126.com.
  • 9 State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. hbzhang@ibms.pumc.edu.cn.
  • # Contributed equally.
PMID: 33850109 DOI: 10.1038/s41392-021-00535-1
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.

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