SOCS3 transactivation by PPARgamma prevents IL-17-driven cancer growth.
Fiche publication
Date publication
juin 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François, Dr LADOIRE Sylvain, Dr VEGRAN Frédérique, Dr REBE Cédric, Dr BRUCHARD Mélanie, Dr HICHAMI Aziz, Dr CHALMIN Fanny, Dr DERANGERE Valentin
Tous les auteurs :
Berger H, Vegran F, Chikh M, Gilardi F, Ladoire S, Bugaut H, Mignot G, Chalmin F, Bruchard M, Derangere V, Chevriaux A, Rebe C, Ryffel B, Pot C, Hichami A, Desvergne B, Ghiringhelli F, Apetoh L
Lien Pubmed
Résumé
Activation of the transcription factor PPARgamma by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARgamma are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARgamma. SOCS3 promoter binding and gene transactivation by PPARgamma was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARgamma by DHA. Furthermore, naive CD4 T cells derived from mice fed a DHA-enriched diet displayed less capability to differentiate into TH17 cells. In two different mouse models of cancer, DHA prevented tumor outgrowth and angiogenesis in an IL-17-dependent manner. Altogether, our results uncover a novel molecular pathway by which PPARgamma-induced SOCS3 expression prevents IL-17-mediated cancer growth.
Référence
Cancer Res. 2013 Jun 15;73(12):3578-90