Liver X receptor beta activation induces pyroptosis of human and murine colon cancer cells.
Fiche publication
Date publication
décembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIREAU Wilfrid, Pr GHIRINGHELLI François, Dr LADOIRE Sylvain, Dr VEGRAN Frédérique, Dr REBE Cédric, Dr BRUCHARD Mélanie, Dr HICHAMI Aziz, Dr CHALMIN Fanny, Dr LIMAGNE Emeric, Dr DERANGERE Valentin
Tous les auteurs :
Derangere V, Chevriaux A, Courtaut F, Bruchard M, Berger H, Chalmin F, Causse SZ, Limagne E, Vegran F, Ladoire S, Simon B, Boireau W, Hichami A, Apetoh L, Mignot G, Ghiringhelli F, Rebe C
Lien Pubmed
Résumé
Liver X receptors (LXRs) have been proposed to have some anticancer properties, through molecular mechanisms that remain elusive. Here we report for the first time that LXR ligands induce caspase-1-dependent cell death of colon cancer cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3 (NLRP3) inflammasome and ATP-mediated P2 x 7 receptor activation. Surprisingly, LXRbeta is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have an antitumoral effect in a mouse colon cancer model, dependent on the presence of LXRbeta, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXRbeta, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis.
Référence
Cell Death Differ. 2014 Dec;21(12):1914-24