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Updated: Feb 5, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGF-β receptors: In and beyond TGF-β signaling
Alexandra Vander Ark1, Jingchen Cao1, Xiaohong Li1
1Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
Abstract:
Transforming growth factor β (TGF-β) plays an important role in normal development and homeostasis. Dysregulation of TGF-β responsiveness and its downstream signaling pathways contribute to many diseases, including cancer initiation, progression, and metastasis. TGF-β ligands bind to three isoforms of the TGF-β receptor (TGFBR) with different affinities. TGFBR1 and 2 are both serine/threonine and tyrosine kinases, but TGFBR3 does not have any kinase activity. They are necessary for activating canonical or noncanonical signaling pathways, as well as for regulating the activation of other signaling pathways. Another prominent feature of TGF-β signaling is its context-dependent effects, temporally and spatially. The diverse effects and context dependency are either achieved by fine-tuning the downstream components or by regulating the expressions and activities of the ligands or receptors. Focusing on the receptors in events in and beyond TGF-β signaling, we review the membrane trafficking of TGFBRs, the kinase activity of TGFBR1 and 2, the direct interactions between TGFBR2 and other receptors, and the novel roles of TGFBR3.
Insights
Transforming growth factor beta (TGF-β) signaling is crucial for development and homeostasis. Dysregulation of TGF-β receptors (TGFBRs) contributes to diseases like cancer, highlighting their complex roles.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- Transforming growth factor beta (TGF-β) is vital for cellular processes and homeostasis.
- Aberrant TGF-β signaling is implicated in cancer initiation, progression, and metastasis.
- TGF-β ligands interact with TGF-β receptors (TGFBRs), which mediate diverse cellular responses.
Purpose of the Study:
- To review the multifaceted roles of TGF-β receptors (TGFBRs) in TGF-β signaling and beyond.
- To explore the membrane trafficking, kinase activities, and interactions of TGFBRs.
- To highlight novel functions and context-dependent regulation of TGF-β signaling via its receptors.
Main Methods:
- Literature review focusing on TGFBR membrane trafficking.
- Analysis of kinase activities of TGFBR1 and TGFBR2.
- Examination of TGFBR2 interactions with other receptors and novel TGFBR3 roles.
Main Results:
- TGFBRs exhibit distinct affinities for TGF-β ligands and possess varying kinase activities (TGFBR1 and 2 are kinases, TGFBR3 is not).
- TGFBRs are essential for canonical and noncanonical signaling pathways and regulate other signaling networks.
- TGF-β signaling effects are context-dependent, modulated by receptor and ligand regulation.
Conclusions:
- TGF-β receptors are central regulators of TGF-β signaling with critical roles in development and disease.
- Understanding TGFBR trafficking, kinase activity, and interactions is key to deciphering TGF-β's context-dependent functions.
- Novel roles of TGFBR3 and receptor interactions offer new therapeutic targets for TGF-β-related pathologies.
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