TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex

Zhiyue Su; Zelong Sun; Zhao Wang; Shengjie Wang; Yuxin Wang; Ersuo Jin; Chang Li; Jun Zhao; Zeyi Liu; Zhengyu Zhou; Yong Wang; Xiaoyan Chen; Xia Liu; Zhe Lei; Hong-Tao Zhang

doi:10.1016/j.celrep.2022.111513

TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex

Cell Rep. 2022 Oct 18;41(3):111513. doi: 10.1016/j.celrep.2022.111513.

Authors

Zhiyue Su¹, Zelong Sun¹, Zhao Wang¹, Shengjie Wang², Yuxin Wang¹, Ersuo Jin¹, Chang Li³, Jun Zhao³, Zeyi Liu⁴, Zhengyu Zhou⁵, Yong Wang¹, Xiaoyan Chen¹, Xia Liu¹, Zhe Lei⁶, Hong-Tao Zhang⁷

Affiliations

¹ Soochow University Laboratory of Cancer Molecular Genetics, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China; Department of Genetics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China.
² Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang 222000, China.
³ Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215006, China.
⁴ Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215006, China.
⁵ Laboratory Animal Center, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China.
⁶ Soochow University Laboratory of Cancer Molecular Genetics, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China; Department of Genetics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: leizhe@suda.edu.cn.
⁷ Soochow University Laboratory of Cancer Molecular Genetics, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China; Department of Genetics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China; Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, Jiangsu 215123, China. Electronic address: htzhang@suda.edu.cn.

PMID: 36261009
DOI: 10.1016/j.celrep.2022.111513

Abstract

The molecular underpinnings of lung adenocarcinoma (LUAD) metastasis remain poorly defined. Here, using human LUAD cell lines, we find that transcriptional intermediary factor 1 γ (TIF1γ) binds to TATA box binding protein (TBP) in competition with TBP-associated factor 15 (TAF15) and impedes TAF15/TBP-mediated interleukin 6 (IL-6) transactivation. TIF1γ modifies TAF15 through multi-mono-ubiquitylation and drives nuclear export of TAF15. Functionally, TAF15 accelerates epithelial-mesenchymal transition (EMT) and metastasis of LUAD cells, acting in just the opposite way as TIF1γ. Low TIF1γ or high TAF15 expression levels are shown in metastatic LUAD specimens and correlate with poor survival of individuals with LUAD. Our findings suggest that the TAF15/TBP complex is required for IL-6 activation-induced EMT and invasion, which are inhibited by TIF1γ. This study highlights the crucial interaction between TIF1γ and the TAF15/TBP complex for regulating EMT and metastasis in LUAD.

Keywords: CP: Cancer; EMT; IL6; LUAD; TAF15; TBP; TIF1γ; metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung*
Epithelial-Mesenchymal Transition
Humans
Interleukin-6
Lung Neoplasms* / pathology
TATA-Binding Protein Associated Factors* / genetics
TATA-Box Binding Protein

Substances

Interleukin-6
TAF15 protein, human
TATA-Binding Protein Associated Factors
TATA-Box Binding Protein
TRIM33 protein, human