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

Zhiyue Su1, Zelong Sun1, Zhao Wang1

  • 1Soochow 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.

Cell Reports
|October 19, 2022
PubMed

Insights

Transcriptional intermediary factor 1 γ (TIF1γ) inhibits lung adenocarcinoma (LUAD) metastasis by blocking TAF15/TBP-mediated IL-6 transactivation. Low TIF1γ and high TAF15 expression correlate with poor LUAD patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The mechanisms driving lung adenocarcinoma (LUAD) metastasis are not fully understood.
  • Identifying key regulators of LUAD cell invasion and epithelial-mesenchymal transition (EMT) is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of transcriptional intermediary factor 1 γ (TIF1γ) in regulating LUAD metastasis.
  • To elucidate the molecular interactions between TIF1γ, TBP-associated factor 15 (TAF15), and TATA box binding protein (TBP) in LUAD.

Main Methods:

  • Utilized human LUAD cell lines for molecular and functional studies.
  • Investigated protein-protein interactions, including TIF1γ binding to TBP and competition with TAF15.
  • Analyzed TAF15 modifications (multi-mono-ubiquitylation) and subcellular localization (nuclear export).
  • Correlated TIF1γ and TAF15 expression levels with LUAD patient survival data.

Main Results:

  • TIF1γ impedes TAF15/TBP-mediated interleukin-6 (IL-6) transactivation by binding to TBP and competing with TAF15.
  • TIF1γ induces TAF15 multi-mono-ubiquitylation and nuclear export.
  • TAF15 promotes EMT and metastasis, while TIF1γ inhibits these processes.
  • Metastatic LUAD specimens show low TIF1γ and high TAF15 expression, correlating with poor survival.

Conclusions:

  • The TAF15/TBP complex is essential for IL-6-induced EMT and invasion in LUAD.
  • TIF1γ acts as an inhibitor of LUAD metastasis by disrupting the TAF15/TBP complex.
  • The TIF1γ-TAF15 interaction is a critical regulator of EMT and metastasis in LUAD, offering potential therapeutic targets.
Keywords:
CP: CancerEMTIL6LUADTAF15TBPTIF1γmetastasis

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