Tumor suppressive role of Sestrin2 during colitis and colon carcinogenesis
- University of Michigan, United States
Abstract
The mTOR complex 1 (mTORC1) and endoplasmic reticulum (ER) stress pathways are critical regulators of intestinal inflammation and colon cancer growth. Sestrins are stress-inducible proteins which suppress both mTORC1 and ER stress; however, the role of Sestrins in colon physiology and tumorigenesis has been elusive due to the lack of studies in human tissues or in appropriate animal models. In this study, we show that human SESN2 expression is elevated in the colon of ulcerative colitis patients but is lost upon p53 inactivation during colon carcinogenesis. In mouse colon, Sestrin2 was critical for limiting ER stress and promoting recovery of epithelial cells after inflammatory injury. During colitis-promoted tumorigenesis, Sestrin2 was shown to be an important mediator of p53's control over mTORC1 signaling and tumor cell growth. These results highlight Sestrin2 as a novel tumor suppressor, whose downregulation can accelerate both colitis and colon carcinogenesis.
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Ethics
Animal experimentation: All animal studies were ethically approved (protocol approval numbers: PRO00005712 and PRO00004019) and overseen by the University Committee on Use and Care of Animals (UCUCA) at the University of Michigan.
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© 2016, Ro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tumor suppressive role of Sestrin2 during colitis and colon carcinogenesis
eLife 5:e12204.
https://doi.org/10.7554/eLife.12204
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