Fiche publication
Date publication
avril 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BLAISE Sébastien
,
Dr DALI-YOUCEF Nassim
,
Dr TOMASETTO Catherine
,
Mme MESSADDEQ Nadia
Tous les auteurs :
Dali-Youcef N, Hnia K, Blaise S, Messaddeq N, Blanc S, Postic C, Valet P, Tomasetto C, Rio MC
Lien Pubmed
Résumé
MMP11 overexpression is a bad prognostic factor in various human carcinomas. Interestingly, this proteinase is not expressed in malignant cells themselves but is secreted by adjacent non-malignant mesenchymal/stromal cells, such as cancer associated fibroblasts (CAFs) and adipocytes (CAAs), which favors cancer cell survival and progression. As MMP11 negatively regulates adipogenesis in vitro, we hypothesized that it may play a role in whole body metabolism and energy homeostasis. We used an in vivo gain- (Mmp11-Tg mice) and loss- (Mmp11-/- mice) of-function approach to address the systemic function of MMP11. Strikingly, MMP11 overexpression protects against type 2 diabetes while Mmp11-/- mice exhibit hallmarks of metabolic syndrome. Moreover, Mmp11-Tg mice were protected from diet-induced obesity and display mitochondrial dysfunction, due to oxidative stress, and metabolic switch from oxidative phosphorylation to aerobic glycolysis. This Warburg-like effect observed in adipose tissues might provide a rationale for the deleterious impact of CAA-secreted MMP11, favouring tumor progression. MMP11 overexpression also leads to increased circulating IGF1 levels and the activation of the IGF1/AKT/FOXO1 cascade, an important metabolic signalling pathway. Our data reveal a major role for MMP11 in controlling energy metabolism, and provide new clues for understanding the relationship between metabolism, cancer progression and patient outcome.
Référence
Sci Rep. 2016 Apr;6:25140
