Involvement of the TGFβ pathway in the regulation of α5 β1 integrins by caveolin-1 in human glioblastoma

Int J Cancer. 2012 Aug 1;131(3):601-11. doi: 10.1002/ijc.26415. Epub 2011 Oct 5.


Caveolin-1 plays a crucial role in the development of cancer and its progression. We previously reported that glioblastoma cells expressing low levels of caveolin-1 exerted a more aggressive phenotype than cells expressing high levels. Such phenotype was due to the induction of α(5) β(1) integrin subsequent to the depletion of caveolin-1. Caveolin-1 was identified as a transcriptional repressor of α(5) β(1) integrin. The current study was designed to identify in vitro, the molecular mechanisms by which caveolin-1 controls α(5) β(1) integrin expression and to determine if a negative correlation between caveolin-1 and α(5) β(1) integrins also exists in biopsies and xenografted human brain tumors. We showed that depletion of caveolin-1 lead to the activation of the TGFβ/TGFβRI/Smad2 pathway which in turn induced the expression of α(5) β(1) integrins. We showed that cells expressing the lowest levels of caveolin-1 but the highest levels of α(5) β(1) integrins and TGFβRI were the most sensitive to a α(5) β(1) integrin antagonist and a TGFβRI inhibitor. Screening human glioma biopsies and human glioblastoma xenografts, we isolated subgroups with either low levels of caveolin-1 but high levels of α(5) β(1) integrin and TGFβRI or high levels of caveolin-1 but low levels of α(5) β(1) integrin and TGFβRI. In conclusion, caveolin-1 controls α(5) β(1) integrin expression through the TGFβ/TGFβRI/Smad2 pathway. The status of caveolin-1/α(5) β(1) integrins/TGFβRI might be a useful marker of the tumor evolution/prognosis as well as a predictor of anti-TGFβ or anti-α(5) β(1) integrin therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Caveolin 1 / metabolism*
  • Cell Line, Tumor
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Humans
  • Integrin alpha5beta1 / antagonists & inhibitors
  • Integrin alpha5beta1 / biosynthesis
  • Integrin alpha5beta1 / metabolism*
  • MAP Kinase Signaling System
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Transcription, Genetic
  • Transforming Growth Factor beta / metabolism*
  • Transplantation, Heterologous


  • Biomarkers, Tumor
  • CAV1 protein, human
  • Caveolin 1
  • Integrin alpha5beta1
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta