TRIM27 mediates STAT3 activation at retromer-positive structures to promote colitis and colitis-associated carcinogenesis

Nature Communications
Hong-Xia ZhangYan-Yi Wang

Abstract

STAT3 is a transcription factor that plays central roles in various physiological processes and its deregulation results in serious diseases including cancer. The mechanisms on how STAT3 activity is regulated remains enigmatic. Here we identify TRIM27 as a positive regulator of II-6-induced STAT3 activation and downstream gene expression. TRIM27 localizes to retromer-positive punctate structures and serves as a critical link for recruiting gp130, JAK1, and STAT3 to and subsequent phosphorylation of STAT3 at the retromer-positive structures. Overexpression of TRIM27 promotes cancer cell growth in vitro and tumor growth in nude mice, whereas knockdown of TRIM27 has opposite effects. Deficiency of TRIM27 significantly impairs dextran sulfate sodium (DSS)-induced STAT3 activation, inflammatory cytokine expression and colitis as well as azoxymethane (AOM)/DSS-induced colitis-associated cancer in mice. These findings reveal a retromer-dependent mechanism for regulation of STAT3 activation, inflammation, and inflammation-associated cancer development.

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Citations

May 8, 2019·Proceedings of the National Academy of Sciences of the United States of America·Zhi-Sheng XuYan-Yi Wang
Mar 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yinfang WangPeng Zhang
Dec 6, 2019·Frontiers in Immunology·Rubén Julio Martínez-Torres, Mathias Chamaillard
Oct 18, 2020·International Journal of Molecular Sciences·Wolfgang EberhardtJosef Pfeilschifter
Apr 29, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·San-Yang ChenShui-Jun Zhang
Dec 31, 2020·Cells·Sara E Hanley, Katrina F Cooper
Apr 16, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jinxi LiuShuxia Liu
Jun 29, 2021·Frontiers in Immunology·Xiuzhi JiaWei Zhao
Sep 17, 2021·Essays in Biochemistry·Zhe YangRohan D Teasdale

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Methods Mentioned

BETA
IECs
genotyping
ubiquitination
ELISA
xenograft
transfection
PCR
confocal microscopy
xenografts

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Excel
GraphPad Prism

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