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.
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GOLM1 通过确保肠道稳态中的 Notch 信号平衡来限制结肠炎和结肠肿瘤的发生
DOI：
10.1038/s41392-021-00535-1
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发表时间：
2021-04-14
影响因子：
39.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Pu Y;Song Y;Zhang M;Long C;Li J;Wang Y;Xu Y;Pan F;Zhao N;Zhang X;Xu Y;Cui J;Wang H;Li Y;Zhao Y;Jin D;Zhang H
肠上皮细胞作为第一道屏障，抵御感染和损伤，介导结肠炎症。结直肠癌常伴有慢性炎症。不同于其众所周知的致癌作用，在许多恶性肿瘤中，我们在这里提出，高尔基体膜蛋白1（GOLM 1，也被称为GP73）通过维持肠上皮屏障抑制结直肠肿瘤的发生。GOLM 1缺陷小鼠对粘膜炎症和结肠炎诱导的上皮损伤易感，从而促进结肠癌。从机制上讲，GOLM 1在肠上皮细胞（IEC）的耗竭导致异常的Notch激活，干扰IEC分化，成熟和谱系承诺在小鼠。药理学抑制Notch途径减轻了GOLM 1缺陷小鼠的上皮病变并抑制了促肿瘤发生性炎症。因此，GOLM 1通过调节Notch信号通路的平衡来维持IEC稳态并保护结肠炎和结肠肿瘤的发生。
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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影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
影响因子：
--
作者：
Dunkin D;Iuga AC;Mimouna S;Harris CL;Haure-Mirande JV;Bozec D;Yeretssian G;Dahan S
通讯作者：
Dahan S
影响因子：
4.8
作者：
Kim, Tae-Hee;Shivdasani, Ramesh A.
通讯作者：
Shivdasani, Ramesh A.
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影响因子：
2.9
作者：
Ding, Xiang;Deng, Gang;Chen, Qianxue
通讯作者：
Chen, Qianxue
影响因子：
50.3
作者：
Jackstadt, Rene;van Hooff, Sander R.;Sansom, Owen J.
通讯作者：
Sansom, Owen J.