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.

Details

Title
TRIM27 mediates STAT3 activation at retromer-positive structures to promote colitis and colitis-associated carcinogenesis
Author
Hong-Xia, Zhang 1 ; Zhi-Sheng Xu 2 ; Lin, Hen 3 ; Li, Mi 3 ; Tian Xia 3 ; Cui, Kaisa 3 ; Su-Yun, Wang 4 ; Li, Youjun 3 ; Hong-Bing, Shu 1   VIAFID ORCID Logo  ; Yan-Yi, Wang 4 

 College of Life Sciences, Wuhan University, Wuhan, China; Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China 
 The Joint Center of Translational Precision Medicine, Guangzhou Institute of Pediatrics, Guangzhou Women and Childrenʼs Medical Center, Guangzhou, China; Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China 
 College of Life Sciences, Wuhan University, Wuhan, China 
 Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China 
Pages
1-16
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2092838858
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.