Involvement of the TGFβ pathway in the regulation of α5 β1 integrins by caveolin-1 in human glioblastoma. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue International Journal of Cancer Année : 2012

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

Résumé

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.

Domaines

Cancer

Dates et versions

hal-00746869 , version 1 (29-10-2012)

Identifiants

Citer

Erika C Cosset, Julien Godet, Natacha Entz-Werlé, Eric Guérin, Dominique Guenot, et al.. Involvement of the TGFβ pathway in the regulation of α5 β1 integrins by caveolin-1 in human glioblastoma.. International Journal of Cancer, 2012, 131 (3), pp.601-611. ⟨10.1002/ijc.26415⟩. ⟨hal-00746869⟩
133 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More