Caveolin-1 differentially regulates the transforming growth factor-ß and epidermal growth factor signaling pathways in MDCK cells.
Biochim Biophys Acta Gen Subj
; 1868(9): 130660, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38871061
ABSTRACT
Caveolin-1 is critical for interacting with the TGF-ß receptor (TGFßR) and EGF receptor (EGFR) signaling, often observed in advanced cancers and tissue fibrosis. However, the mechanism underlying caveolin-1-mediated transactivation of TGFßR and EGFR signaling remains unclear. Therefore, we sought to determine whether caveolin-1 is involved in canonical and non-canonical TGFßR and EGFR signaling transactivation in this study. Methyl-ß-cyclodextrin (MßCD) 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 TGFßR and EGFR canonical signaling. On the contrary, caveolin-1 inhibited TGF-ß1-induced ERK2 activation independent of tyrosine 14 phosphorylation. Although EGF failed to induce Smad3 phosphorylation in caveolin-1 knockdown cells, it activated Smad3 upon MßCD co-treatment, indicating that caveolin-1 indirectly regulated the non-canonical pathway of EGF. In conclusion, caveolin-1 differentially modulates TGFßR and EGFR signaling. Thus, targeting caveolin-1 is a potential strategy for treating diseases involving TGF-ß1 and EGF signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transducción de Señal
/
Caveolina 1
/
Receptores ErbB
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Gen Subj
/
Biochim. biophys. acta, Gen. subj
/
Biochimica et biophysica acta. G, General subjects (Print)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Taiwán