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Updated: Jun 4, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
The TGF-β co-receptor, CD109, promotes internalization and degradation of TGF-β receptors
Albane A Bizet1, Kai Liu, Nicolas Tran-Khanh
1Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, QC, Canada.
Abstract:
Transforming growth factor-β (TGF-β) is implicated in numerous pathological disorders, including cancer and mediates a broad range of biological responses by signaling through the type I and II TGF-β receptors. Internalization of these receptors via the clathrin-coated pits pathway facilitates SMAD-mediated signaling, whereas internalization via the caveolae pathway is associated with receptor degradation. Thus, molecules that modulate receptor endocytosis are likely to play a critical role in regulating TGF-β action. We previously identified CD109, a GPI-anchored protein, as a TGF-β co-receptor and a negative regulator of TGF-β signaling. Here, we demonstrate that CD109 associates with caveolin-1, a major component of the caveolae. Moreover, CD109 increases binding of TGF-β to its receptors and enhances their internalization via the caveolae. In addition, CD109 promotes localization of the TGF-β receptors into the caveolar compartment in the presence of ligand and facilitates TGF-β-receptor degradation. Thus, CD109 regulates TGF-β receptor endocytosis and degradation to inhibit TGF-β signaling. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Insights
CD109, a transforming growth factor-β (TGF-β) co-receptor, regulates TGF-β receptor endocytosis and degradation. This mechanism inhibits TGF-β signaling, impacting various pathological disorders like cancer.
Area of Science:
- Cell biology
- Molecular signaling
- Cancer research
Background:
- Transforming growth factor-β (TGF-β) signaling is crucial in numerous diseases, including cancer.
- TGF-β receptor endocytosis pathways (clathrin-coated pits vs. caveolae) differentially regulate signaling and degradation.
- CD109 was previously identified as a TGF-β co-receptor and negative regulator of TGF-β signaling.
Purpose of the Study:
- To elucidate the mechanism by which CD109 regulates TGF-β receptor trafficking and signaling.
- To investigate the association between CD109, caveolae, and TGF-β receptor endocytosis.
Main Methods:
- Co-immunoprecipitation to assess CD109 and caveolin-1 association.
- Confocal microscopy to visualize receptor localization.
- Ligand-binding assays and receptor degradation studies.
Main Results:
- CD109 associates with caveolin-1, a key component of caveolae.
- CD109 enhances TGF-β binding to its receptors and promotes their caveolae-mediated internalization.
- CD109 facilitates TGF-β receptor localization within caveolae and subsequent degradation, thereby inhibiting signaling.
Conclusions:
- CD109 acts as a negative regulator of TGF-β signaling by modulating receptor endocytosis and degradation via the caveolae pathway.
- Targeting CD109-mediated endocytosis could offer therapeutic strategies for TGF-β-related pathologies, including cancer.
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