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Updated: May 8, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis

Long Zhang1, Fangfang Zhou, Amaya García de Vinuesa

  • 1Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands; Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Molecular Cell
|August 27, 2013
PubMed

Insights

Tumor necrosis factor receptor-associated factor 4 (TRAF4) promotes cancer by enhancing transforming growth factor beta (TGF-β) signaling. TRAF4 drives TGF-β-induced cell migration and metastasis, indicating its role in breast cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Transforming growth factor beta (TGF-β) signaling is a critical pathway implicated in advanced cancers.
  • Targeting TGF-β signaling presents a therapeutic strategy for cancer treatment.

Purpose of the Study:

  • To identify key mediators of pro-oncogenic TGF-β signaling.
  • To investigate the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in TGF-β-induced oncogenic processes.

Main Methods:

  • Investigated TRAF4's interaction with the TGF-β receptor complex.
  • Assessed the impact of TRAF4 on E3 ligase SMURF2 and deubiquitinase USP15 recruitment.
  • Analyzed TGF-β-activated kinase 1 (TAK1) activation and TRAF4 polyubiquitylation.
  • Correlated TRAF4 expression with patient prognosis and signaling markers.

Main Results:

  • TRAF4 antagonizes SMURF2 and recruits USP15 to the TGF-β type I receptor (TβRI), stabilizing it.
  • TRAF4 interaction with TGF-β receptor triggers Lys 63-linked polyubiquitylation and TAK1 activation.
  • TRAF4 is essential for TGF-β-induced migration, epithelial-to-mesenchymal transition, and metastasis.
  • Elevated TRAF4 expression correlates with increased pSMAD2, pTAK1, and poor breast cancer prognosis.

Conclusions:

  • TRAF4 is a crucial regulator of TGF-β signaling in cancer.
  • TRAF4 enhances TGF-β-mediated oncogenic signaling, contributing to breast cancer pathogenesis and metastasis.

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