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

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.

• Authors: 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
• Journal: Cell reports (Cell Rep) Vol. 41 Issue 3 Pg. 111513 (10 18 2022) ISSN: 2211-1247 [Electronic] United States
• PMID: 36261009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Humans
• Adenocarcinoma of Lung
• Epithelial-Mesenchymal Transition
• Interleukin-6
• Lung Neoplasms (pathology)
• TATA-Binding Protein Associated Factors (genetics)
• TATA-Box Binding Protein