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Updated: Dec 23, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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TrkB-Induced Inhibition of R-SMAD/SMAD4 Activation is Essential for TGF-β-Mediated Tumor Suppressor Activity

Min Soo Kim1, Wook Jin1

  • 1Laboratory of Molecular Disease and Cell Regulation, Department of Biochemistry, School of Medicine, Gachon University, Incheon 21999, Korea.

Cancers
|April 29, 2020
PubMed

Insights

Tropomyosin receptor kinase B (TrkB) disrupts transforming growth factor-beta (TGF-β) tumor suppression by inhibiting SMAD complex formation. Restoring TrkB levels reactivates TGF-β

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • TrkB activation of IL6/JAK2/STAT3 pathway promotes epithelial-mesenchymal transition (EMT) and tumor metastasis.
  • Transforming growth factor-beta (TGF-β) typically suppresses tumors via the SMAD signaling pathway.
  • The interplay between TrkB and TGF-β signaling in tumor suppression remains largely unexplored.

Purpose of the Study:

  • To investigate the role of TrkB in modulating TGF-β-mediated tumor suppression.
  • To elucidate the molecular mechanisms by which TrkB interferes with TGF-β signaling.

Main Methods:

  • Investigated TrkB kinase activity and its impact on TGF-β signaling components.
  • Analyzed TrkB-SMAD interactions using co-immunoprecipitation and cellular assays.
  • Assessed the effect of TrkB knockdown on TGF-β target gene expression and tumor suppressor activity.

Main Results:

  • TrkB was identified as a key inhibitor of TGF-β-mediated tumor suppression.
  • TrkB directly interacts with SMAD proteins, preventing R-SMAD/SMAD4 complex formation.
  • This interaction suppresses TGF-β-induced nuclear translocation and target gene expression.
  • Knockdown of TrkB restored the tumor inhibitory effects of TGF-β signaling.

Conclusions:

  • TrkB antagonizes TGF-β's tumor suppressor function through direct interaction with SMADs.
  • Targeting TrkB-SMAD interactions may represent a novel therapeutic strategy to restore TGF-β tumor suppressor activity in cancer.
Keywords:
TrkBtransforming growth factor-β (TGF-β)tumor progressiontumor suppressor activity

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