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Liver X receptor ? activation induces pyroptosis of human and murine colon cancer cells.

ABSTRACT: 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 × 7 receptor activation. Surprisingly, LXR? 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 LXR?, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXR?, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis.

SUBMITTER: Derangere V 

PROVIDER: S-EPMC4227150 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells.

Derangère V V   Chevriaux A A   Courtaut F F   Bruchard M M   Berger H H   Chalmin F F   Causse S Z SZ   Limagne E E   Végran F F   Ladoire S S   Simon B B   Boireau W W   Hichami A A   Apetoh L L   Mignot G G   Ghiringhelli F F   Rébé C C  

Cell death and differentiation 20140815 12

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 × 7 receptor activation. Surprisingly, LXRβ is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leadin  ...[more]

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