ArticleCell death & disease2014
Caveolin-1 is required for TGF-β-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 61 citations in OpenAlex.
- Caveolae in cancer: mechanochemical signaling in tumor progression, immunity, and therapy.Cell communication and signaling : CCS · 2026Review
- Proactive and reactive roles of TGF-β in cancer.Seminars in cancer biology · 2023Review
- Tetraspanin 8 Subfamily Members Regulate Substrate-Specificity of a Disintegrin and Metalloprotease 17.Cells · 2022Article
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.Science (New York, N.Y.) · 2022Article
- The TGF-β/NADPH Oxidases Axis in the Regulation of Liver Cell Biology in Health and Disease.Cells · 2021Review
- Review
- Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin1 in hepatic stellate cells.Stem cell research & therapy · 2021Article
- Comparative Metabolomics and Proteomics RevealFrontiers in immunology · 2021Article
- A novel TGF-β receptor II mutation (I227T/N236D) promotes aggressive phenotype of oral squamous cell carcinoma via enhanced EGFR signaling.BMC cancer · 2020Article
- The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Involvement of the TGF-β1 pathway in caveolin-1-associated regulation of head and neck tumor cell metastasis.Oncology letters · 2020Article
- Review
- Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by regulating endocytotic recycling of epidermal growth factor receptor.Oncology letters · 2018Article
- TGF-β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways.Molecular oncology · 2018Article
- The level of caveolin-1 expression determines response to TGF-β as a tumour suppressor in hepatocellular carcinoma cells.Cell death & disease · 2017Article
- Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation.Oncology letters · 2017Article
- Caveolin-1 in the Pathogenesis of Diabetic Nephropathy: Potential Therapeutic Target?Current diabetes reports · 2017Review
- TIMPs: versatile extracellular regulators in cancer.Nature reviews. Cancer · 2017Review
- Microparticle-Induced Activation of the Vascular Endothelium Requires Caveolin-1/Caveolae.PloS one · 2016Article
- Caveolin-1 Expression Ameliorates Nephrotic Damage in a Rabbit Model of Cholesterol-Induced Hypercholesterolemia.PloS one · 2016Article
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-beta (TGF-β) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, whose balance decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β in these cells. Caveolin-1 (Cav1) is a structural protein of caveolae linked to TGF-β receptors trafficking and signaling. Previous results have indicated that in hepatocytes, Cav1 is required for TGF-β-induced anti-apoptotic signals, but the molecular mechanism is not fully understood yet. In this work, we show that immortalized Cav1(-/-) hepatocytes were more sensitive to the pro-apoptotic effects induced by TGF-β, showing a higher activation of caspase-3, higher decrease in cell viability and prolonged increase through time of intracellular reactive oxygen species (ROS). These results were coincident with attenuation of TGF-β-induced survival signals in Cav1(-/-) hepatocytes, such as AKT and ERK1/2 phosphorylation and NFκ-B activation. Transactivation of the EGFR pathway by TGF-β was impaired in Cav1(-/-) hepatocytes, which correlated with lack of activation of TACE/ADAM17, the metalloprotease responsible for the shedding of EGFR ligands. Reconstitution of Cav1 in Cav1(-/-) hepatocytes rescued wild-type phenotype features, both in terms of EGFR transactivation and TACE/ADAM17 activation. TACE/ADAM17 was localized in detergent-resistant membrane (DRM) fractions in Cav1(+/+) cells, which was not the case in Cav1(-/-) cells. Disorganization of lipid rafts after treatment with cholesterol-binding agents caused loss of TACE/ADAM17 activation after TGF-β treatment. In conclusion, in hepatocytes, Cav1 is required for TGF-β-mediated activation of the metalloprotease TACE/ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGF-β pro-apoptotic effects. Therefore, Cav1 contributes to the pro-tumorigenic effects of TGF-β in liver cancer cells.
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