Titre
Rapamycin-mediated FOXO1 inactivation reduces the anticancer efficacy of rapamycin.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Abdelnour-Berchtold, E.
Auteure/Auteur
Cerantola, Y.
Auteure/Auteur
Roulin, D.
Auteure/Auteur
Dormond-Meuwly, A.
Auteure/Auteur
Demartines, N.
Auteure/Auteur
Dormond, O.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1791-7530[electronic], 0250-7005[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
30
Numéro
3
Première page
799
Dernière page/numéro d’article
804
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors such as rapamycin have shown modest effects in cancer therapy due in part to the removal of a negative feedback loop leading to the activation of the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathway. In this report, we have investigated the role of FOXO1, a downstream substrate of the PI3K/Akt pathway in the anticancer efficacy of rapamycin. MATERIALS AND METHODS: Colon cancer cells were treated with rapamycin and FOXO1 phosphorylation was determined by Western blot. Colon cancer cells transfected with a constitutively active mutant of FOXO1 or a control plasmid were treated with rapamycin and the antiproliferative efficacy of rapamycin was monitored. RESULTS: Rapamycin induced the phosphorylation of FOXO1 as well as its translocation from the nucleus to the cytoplasm, leading to FOXO1 inactivation. The expression of an active mutant of FOXO1 in colon cancer cells potentiated the antiproliferative efficacy of rapamycin in vitro and its antitumor efficacy in vivo. CONCLUSION: Taken together these results show that rapamycin-induced FOXO1 inactivation reduces the antitumor efficacy of rapamycin.
Sujets
PID Serval
serval:BIB_FD962EA99103
PMID
Date de création
2010-06-28T16:11:46.955Z
Date de création dans IRIS
2025-05-21T07:14:30Z