ArticlePLoS biology2015
ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-β-Induced Smad Activation.
Article in PLoS biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- MicroRNA-29b-5p regulates cell proliferation and cancer stemness via TGF-β/p300 pathway in human synovial sarcoma.Cancer cell international · 2026Article
- Investigating the Impact of the Secretome From hAMSCs on HT-29 Colon Cancer Cells via TNF-α/TGF-β/c-MYC Signaling Pathways Using a Three-Dimensional Cell Culture Model.Immunity, inflammation and disease · 2025Article
- Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways.Journal of clinical and translational hepatology · 2025Review
- Epithelial Cell Dysfunction in Pulmonary Fibrosis: Mechanisms, Interactions, and Emerging Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The pivotal role of TGF-β/Smad pathway in fibrosis pathogenesis and treatment.Frontiers in oncology · 2025Review
- High expression of SLC7A1 in high-grade serous ovarian cancer promotes tumor progression and is involved in MAPK/ERK pathway and EMT.Cancer medicine · 2024Article
- Tonic ErbB signaling underlies TGFβ-induced activation of ERK and is required for lens cell epithelial to myofibroblast transition.Molecular biology of the cell · 2024Article
- The Antioxidative Effects of Flavones in Hypertensive Disease.Biomedicines · 2023Review
- LY6K depletion modulates TGF-β and EGF signaling.Cancer medicine · 2023Article
- Review
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- Targeting Breast Cancer Stem Cells Using Naturally Occurring Phytoestrogens.International journal of molecular sciences · 2022Review
- Targeting TGF-β signal transduction for fibrosis and cancer therapy.Molecular cancer · 2022Review
- Article
- Article
- GABARAP suppresses EMT and breast cancer progression via the AKT/mTOR signaling pathway.Aging · 2021Article
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Alleviate PM2.5-Induced Lung Injury and Pulmonary Fibrosis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Transforming growth factor-β (TGF-β)-induced up-regulation of TGF-β receptors at the cell surface amplifies the TGF-β response.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Epithelial-mesenchymal transition (EMT) is a normal cell differentiation event during development and contributes pathologically to carcinoma and fibrosis progression. EMT often associates with increased transforming growth factor-β (TGF-β) signaling, and TGF-β drives EMT, in part through Smad-mediated reprogramming of gene expression. TGF-β also activates the Erk MAPK pathway through recruitment and Tyr phosphorylation of the adaptor protein ShcA by the activated TGF-β type I receptor. We found that ShcA protects the epithelial integrity of nontransformed cells against EMT by repressing TGF-β-induced, Smad-mediated gene expression. p52ShcA competed with Smad3 for TGF-β receptor binding, and down-regulation of ShcA expression enhanced autocrine TGF-β/Smad signaling and target gene expression, whereas increased p52ShcA expression resulted in decreased Smad3 binding to the TGF-β receptor, decreased Smad3 activation, and increased Erk MAPK and Akt signaling. Furthermore, p52ShcA sequestered TGF-β receptor complexes to caveolin-associated membrane compartments, and reducing ShcA expression enhanced the receptor localization in clathrin-associated membrane compartments that enable Smad activation. Consequently, silencing ShcA expression induced EMT, with increased cell migration, invasion, and dissemination, and increased stem cell generation and mammosphere formation, dependent upon autocrine TGF-β signaling. These findings position ShcA as a determinant of the epithelial phenotype by repressing TGF-β-induced Smad activation through differential partitioning of receptor complexes at the cell surface.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.