1. Caveolin-1 differentially regulates the transforming growth factor-β and epidermal growth factor signaling pathways in MDCK cells.
- Author
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Hsiao SC, Liao WH, Chang HA, Lai YS, Chan TW, Chen YC, and Chiu WT
- Subjects
- Animals, Dogs, Madin Darby Canine Kidney Cells, Phosphorylation, Epidermal Growth Factor metabolism, Epidermal Growth Factor pharmacology, Transforming Growth Factor beta metabolism, Receptors, Transforming Growth Factor beta metabolism, Humans, Transforming Growth Factor beta1 metabolism, Caveolin 1 metabolism, Caveolin 1 genetics, Signal Transduction, ErbB Receptors metabolism
- Abstract
Caveolin-1 is critical for interacting with the TGF-β receptor (TGFβR) and EGF receptor (EGFR) signaling, often observed in advanced cancers and tissue fibrosis. However, the mechanism underlying caveolin-1-mediated transactivation of TGFβR and EGFR signaling remains unclear. Therefore, we sought to determine whether caveolin-1 is involved in canonical and non-canonical TGFβR and EGFR signaling transactivation in this study. Methyl-β-cyclodextrin (MβCD) was used to disrupt the cholesterol-containing membranes domains, and the caveolin-1 scaffolding domain (CSD) peptide was used to mimic the CSD of caveolin-1. Additionally, we transfected the Madin-Darby canine kidney cells with wild-type or phosphorylation-defective caveolin-1. We discovered that tyrosine 14 of caveolin-1 was critical for the negative regulation of TGFβR and EGFR canonical signaling. On the contrary, caveolin-1 inhibited TGF-β1-induced ERK2 activation independent of tyrosine 14 phosphorylation. Although EGF failed to induce Smad3 phosphorylation in caveolin-1 knockdown cells, it activated Smad3 upon MβCD co-treatment, indicating that caveolin-1 indirectly regulated the non-canonical pathway of EGF. In conclusion, caveolin-1 differentially modulates TGFβR and EGFR signaling. Thus, targeting caveolin-1 is a potential strategy for treating diseases involving TGF-β1 and EGF signaling., Competing Interests: Declaration of competing interest The authors declare there are no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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