Fiche publication
Date publication
août 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHOULIER Laurence
,
Dr DONTENWILL Monique
,
Pr LEHMANN Maxime
,
Dr MARTIN Sophie
Tous les auteurs :
Janouskova H, Ray AM, Noulet F, Lelong-Rebel I, Choulier L, Schaffner F, Lehmann M, Martin S, Teisinger J, Dontenwill M
Lien Pubmed
Résumé
Integrins emerge nowadays as crucial actors of tumor aggressiveness and resistance to therapies. Integrin alpha5beta1, the fibronectin receptor, determines malignant properties of colon carcinoma which is one of the most important causes of cancer-related deaths in the world. Here we show that inhibition of alpha5 integrin subunit expression by siRNA or alpha5beta1 integrin function by specific antagonist affects the survival of HCT116 colon cancer cells. We also evidence that pharmacological reactivation of the tumor suppressor p53 by Nutlin-3a inhibits specifically the expression of the alpha5 integrin subunit both at the transcriptional and protein level. Inversely repression of alpha5 integrin modulates p53 activity. A clear relationship between p53 activation by Nutlin-3a, alpha5 repression and cell survival is shown. No such effects are obtained in cells lacking p53 or when another non-genotoxic activator of p53, RITA, is used. Our results emphasize the crucial role of alpha5beta1 integrin in colon tumors. Data also suggest that interfering with the integrin alpha5beta1 through the reactivation of p53 by Nutlin-3a may be of valuable interest as a new therapeutic option for colon tumors expressing high level of the integrin and a wild type p53.
Référence
Cancer Lett. 2013 Aug 19;336(2):307-18
