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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
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
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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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