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Caveolin-1 differentially regulates the transforming growth factor-β and epidermal growth factor signaling pathways

Shih-Chuan Hsiao1, Wei-Hsiang Liao2, Heng-Ai Chang3

  • 1Department of Hematology & Oncology, Saint Martin de Porres Hospital, Chiayi 600, Taiwan.

Biochimica Et Biophysica Acta. General Subjects
|June 13, 2024
PubMed

Insights

Caveolin-1 differentially regulates TGF-β receptor (TGFβR) and EGF receptor (EGFR) signaling pathways. Targeting caveolin-1 may offer a therapeutic strategy for fibrosis and cancer.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Cancer research

Background:

  • Caveolin-1 interacts with TGF-β receptor (TGFβR) and EGF receptor (EGFR) signaling.
  • This interaction is implicated in advanced cancers and tissue fibrosis.
  • The precise mechanism of caveolin-1's role in TGFβR and EGFR signaling remains unclear.

Purpose of the Study:

  • To investigate caveolin-1's involvement in canonical and non-canonical TGFβR and EGFR signaling transactivation.
  • To elucidate the specific mechanisms by which caveolin-1 modulates these signaling pathways.

Main Methods:

  • Disruption of cholesterol-rich membrane domains using Methyl-β-cyclodextrin (MβCD).
  • Mimicking the caveolin-1 scaffolding domain (CSD) using a CSD peptide.
  • Transfection of Madin-Darby canine kidney cells with wild-type or phosphorylation-defective caveolin-1.

Main Results:

  • Tyrosine 14 of caveolin-1 is crucial for the negative regulation of canonical TGFβR and EGFR signaling.
  • Caveolin-1 inhibited TGF-β1-induced ERK2 activation independently of tyrosine 14 phosphorylation.
  • Caveolin-1 indirectly regulated EGF's non-canonical pathway, as evidenced by Smad3 phosphorylation changes.

Conclusions:

  • Caveolin-1 exhibits differential modulation of TGFβR and EGFR signaling pathways.
  • Targeting caveolin-1 presents a potential therapeutic strategy for diseases involving TGF-β1 and EGF signaling, such as cancer and fibrosis.
Keywords:
Caveolin-1Caveolin-1 scaffolding domainEpidermal growth factorNon-canonical pathwayTransactivationTransforming growth factor-β

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