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Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805551/ https://www.ncbi.nlm.nih.gov/pubmed/26913956 http://dx.doi.org/10.7554/eLife.12204 |
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author | Ro, Seung-Hyun Xue, Xiang Ramakrishnan, Sadeesh K Cho, Chun-Seok Namkoong, Sim Jang, Insook Semple, Ian A Ho, Allison Park, Hwan-Woo Shah, Yatrik M Lee, Jun Hee |
author_facet | Ro, Seung-Hyun Xue, Xiang Ramakrishnan, Sadeesh K Cho, Chun-Seok Namkoong, Sim Jang, Insook Semple, Ian A Ho, Allison Park, Hwan-Woo Shah, Yatrik M Lee, Jun Hee |
author_sort | Ro, Seung-Hyun |
collection | PubMed |
description | 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 the 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. DOI: http://dx.doi.org/10.7554/eLife.12204.001 |
format | Online Article Text |
id | pubmed-4805551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-48055512016-03-25 Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis Ro, Seung-Hyun Xue, Xiang Ramakrishnan, Sadeesh K Cho, Chun-Seok Namkoong, Sim Jang, Insook Semple, Ian A Ho, Allison Park, Hwan-Woo Shah, Yatrik M Lee, Jun Hee eLife Cell Biology 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 the 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. DOI: http://dx.doi.org/10.7554/eLife.12204.001 eLife Sciences Publications, Ltd 2016-02-25 /pmc/articles/PMC4805551/ /pubmed/26913956 http://dx.doi.org/10.7554/eLife.12204 Text en © 2016, Ro et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Ro, Seung-Hyun Xue, Xiang Ramakrishnan, Sadeesh K Cho, Chun-Seok Namkoong, Sim Jang, Insook Semple, Ian A Ho, Allison Park, Hwan-Woo Shah, Yatrik M Lee, Jun Hee Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
title | Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
title_full | Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
title_fullStr | Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
title_full_unstemmed | Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
title_short | Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
title_sort | tumor suppressive role of sestrin2 during colitis and colon carcinogenesis |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805551/ https://www.ncbi.nlm.nih.gov/pubmed/26913956 http://dx.doi.org/10.7554/eLife.12204 |
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