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TGF-β signaling in diseases
Research Guide
What is TGF-β signaling in diseases?
TGF-β signaling in diseases refers to the Transforming Growth Factor Beta (TGF-β) pathway's roles in pathology through Smad-dependent and Smad-independent mechanisms that drive tumor suppression, cancer progression, epithelial-mesenchymal transition (EMT), metastasis, angiogenesis, immune response modulation, and extracellular matrix remodeling.
The field encompasses 38,406 papers on TGF-β signaling's involvement in Smad-dependent and Smad-independent pathways, tumor suppression, cancer progression, BMP signaling, immune response, cell differentiation, metastasis, EMT regulation, and angiogenesis. Key works detail receptor serine/threonine kinases forming a signal transduction network controlling tissue development and homeostasis. TGF-β inhibitors are explored for therapeutic use in diseases like cancer.
Topic Hierarchy
Research Sub-Topics
Smad-Dependent TGF-β Signaling
This sub-topic dissects canonical TGF-β pathway activation via Smad2/3 phosphorylation, nuclear translocation, and target gene regulation. Researchers study pathway dynamics in development and fibrosis.
TGF-β in Epithelial-Mesenchymal Transition
This sub-topic investigates TGF-β induction of EMT through transcription factors like Snail and ZEB in carcinoma progression. Studies explore partial EMT states and reversibility in metastasis.
TGF-β Tumor Suppression Mechanisms
This sub-topic examines TGF-β's early cytostatic effects via cell cycle arrest and apoptosis in premalignant cells. Researchers analyze context-dependent switches to tumor promotion.
Non-Smad TGF-β Pathways
This sub-topic covers Smad-independent signaling through MAPK, PI3K, and Rho GTPases in TGF-β responses. Research links these arms to inflammation, motility, and angiogenesis.
TGF-β Inhibitors in Cancer Therapy
This sub-topic evaluates small molecules, antibodies, and traps blocking TGF-β ligands or receptors in clinical trials. Researchers assess efficacy, toxicity, and combination strategies.
Why It Matters
TGF-β signaling influences cancer progression by enabling the angiogenic switch during tumorigenesis, as shown in "Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis" (Hanahan and Folkman, 1996), where tumor cells acquire vascular support essential for growth beyond 1-2 mm³. In metastasis, it drives epithelial-mesenchymal transition via molecular mechanisms outlined in "Molecular mechanisms of epithelial–mesenchymal transition" (Lamouille et al., 2014), allowing cancer cells to invade and disseminate. Matrix crosslinking enhanced by TGF-β signaling promotes tumor progression through integrin signaling, per "Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling" (Levental et al., 2009), with implications for fibrosis and bone diseases linked to BMP pathways in "Novel Regulators of Bone Formation: Molecular Clones and Activities" (Wozney et al., 1988). These roles support development of TGF-β inhibitors targeting EMT and angiogenesis in oncology.
Reading Guide
Where to Start
"TGF-β SIGNAL TRANSDUCTION" (Massagué, 1998) provides the foundational overview of the signal transduction network involving receptor kinases, ideal for beginners to grasp core mechanisms before specifics.
Key Papers Explained
"TGF-β SIGNAL TRANSDUCTION" (Massagué, 1998) establishes the basic network, extended by "Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus" (Shi and Massagué, 2003) detailing nuclear translocation and "Smad-dependent and Smad-independent pathways in TGF-β family signalling" (Derynck and Zhang, 2003) differentiating pathway branches. "Molecular mechanisms of epithelial–mesenchymal transition" (Lamouille et al., 2014) applies these to EMT in disease, while "TGFβ in Cancer" (Massagué, 2008) synthesizes cancer contexts. "Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis" (Hanahan and Folkman, 1996) connects to vascular aspects.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Recent works build on EMT and matrix remodeling from "Remodelling the extracellular matrix in development and disease" (Bonnans et al., 2014) and "Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling" (Levental et al., 2009), focusing on integrin-TGF-β crosstalk in fibrosis and metastasis models. BMP applications in bone formation per "Novel Regulators of Bone Formation: Molecular Clones and Activities" (Wozney et al., 1988) inform orthopedics.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Molecular mechanisms of epithelial–mesenchymal transition | 2014 | Nature Reviews Molecul... | 8.0K | ✓ |
| 2 | TGF-β SIGNAL TRANSDUCTION | 1998 | Annual Review of Bioch... | 7.6K | ✕ |
| 3 | Patterns and Emerging Mechanisms of the Angiogenic Switch duri... | 1996 | Cell | 6.9K | ✓ |
| 4 | Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus | 2003 | Cell | 5.8K | ✓ |
| 5 | Smad-dependent and Smad-independent pathways in TGF-β family s... | 2003 | Nature | 5.3K | ✕ |
| 6 | Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differen... | 1997 | Cell | 4.2K | ✓ |
| 7 | Remodelling the extracellular matrix in development and disease | 2014 | Nature Reviews Molecul... | 4.1K | ✓ |
| 8 | Matrix Crosslinking Forces Tumor Progression by Enhancing Inte... | 2009 | Cell | 3.9K | ✓ |
| 9 | Novel Regulators of Bone Formation: Molecular Clones and Activ... | 1988 | Science | 3.9K | ✕ |
| 10 | TGFβ in Cancer | 2008 | Cell | 3.8K | ✓ |
Frequently Asked Questions
What are the main pathways in TGF-β signaling?
TGF-β signaling operates through Smad-dependent pathways involving receptor serine/threonine kinases and Smad-independent pathways. "Smad-dependent and Smad-independent pathways in TGF-β family signalling" (Derynck and Zhang, 2003) details how both mediate responses from cell membrane to nucleus. "Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus" (Shi and Massagué, 2003) describes the network controlling tissue homeostasis.
How does TGF-β signaling contribute to cancer?
"TGFβ in Cancer" (Massagué, 2008) explains TGF-β's dual role in tumor suppression and progression. It drives metastasis and angiogenesis, as in "Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis" (Hanahan and Folkman, 1996). Inhibitors target these effects for therapy.
What is the role of TGF-β in epithelial-mesenchymal transition?
"Molecular mechanisms of epithelial–mesenchymal transition" (Lamouille et al., 2014) outlines TGF-β-induced EMT in development and fibrosis. This process enables cell migration and invasion in cancer metastasis. It involves Smad signaling and extracellular matrix remodeling.
How does TGF-β signaling affect the extracellular matrix in disease?
"Remodelling the extracellular matrix in development and disease" (Bonnans et al., 2014) links TGF-β to matrix changes in cancer and fibrosis. "Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling" (Levental et al., 2009) shows how it enhances integrin signaling to promote tumors.
What is the connection between TGF-β and BMP signaling?
BMP signaling, part of the TGF-β family, induces bone formation as in "Novel Regulators of Bone Formation: Molecular Clones and Activities" (Wozney et al., 1988). "TGF-β SIGNAL TRANSDUCTION" (Massagué, 1998) describes shared receptor mechanisms. "Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation" (Ducy et al., 1997) links it to osteoblast differentiation.
What are current therapeutic approaches targeting TGF-β signaling?
TGF-β inhibitors are developed to block progression in cancer and fibrosis. Papers highlight targeting Smad pathways and EMT regulation. The field explores interventions based on transduction networks from "TGF-β SIGNAL TRANSDUCTION" (Massagué, 1998).
Open Research Questions
- ? How do Smad-independent pathways interact with Smad-dependent ones to fine-tune TGF-β responses in specific cancers?
- ? What mechanisms allow TGF-β to switch from tumor suppression to promotion during tumorigenesis?
- ? How does TGF-β-mediated extracellular matrix remodeling quantitatively influence integrin signaling strength in metastasis?
- ? What are the precise roles of BMP subfamily members in TGF-β-driven bone diseases beyond osteoblast differentiation?
- ? How can TGF-β inhibitors selectively target pathological EMT without disrupting normal development?
Recent Trends
The field maintains 38,406 works with sustained focus on Smad pathways, EMT, and inhibitors, as evidenced by high citations of "Molecular mechanisms of epithelial–mesenchymal transition" (Lamouille et al., 2014; 7958 citations) and "Remodelling the extracellular matrix in development and disease" (Bonnans et al., 2014; 4149 citations).
No new preprints or news in the last 6-12 months indicate steady maturation rather than rapid shifts.
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