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Updated: Jul 3, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Transforming growth factor-β receptors: versatile mechanisms of ligand activation

Zheng-Jie Chia1,2,3, Ying-Nan Cao4, Peter J Little1,4

  • 1School of Pharmacy, The University of Queensland, Brisbane, QLD, 4102, Australia.

Acta Pharmacologica Sinica
|February 13, 2024
PubMed

Insights

Transforming growth factor-β (TGF-β) receptor activation initiates signaling pathways. Understanding these diverse activation mechanisms offers potential therapeutic targets for pathological conditions.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Transforming growth factor-β (TGF-β) signaling is crucial for cellular functions.
  • Dysregulation of TGF-β pathways is linked to various pathological conditions.
  • TGF-β signaling begins with the activation of transmembrane TGF-β receptors (TGFBR).

Purpose of the Study:

  • To provide a comprehensive review of the diverse mechanisms of TGFBR activation.
  • To highlight the cell-type and agonist selectivity in TGFBR activation.
  • To explore potential therapeutic targets for modulating TGF-β signaling.

Main Methods:

  • Review of existing literature on TGF-β signaling and TGFBR activation.
  • Analysis of molecular mechanisms involved in TGF-β ligand liberation and receptor activation.
  • Examination of cell surface components and cross-talk with other signaling pathways.

Main Results:

  • TGFBR activation involves intricate mechanisms, including ligand liberation from latent forms.
  • Cell surface compartments utilize thrombospondins, integrins, MMPs, and ROS for active TGF-β release.
  • TGFBR activation can be initiated by other signaling pathways, indicating complex cross-talk.
  • Mechanisms exhibit selectivity based on cell type, agonists, and TGF-β isoforms.

Conclusions:

  • TGFBR activation is a highly regulated process with diverse contributing mechanisms.
  • Understanding these mechanisms reveals potential therapeutic strategies for diseases associated with TGF-β pathway dysregulation.
  • Further exploration of these pathways can lead to novel therapeutic interventions.
Keywords:
TGFBRintegrinsmatrix metalloproteinasesreceptor Smadsthrombospondinstransactivation

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