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Cell Death Differ. 2014 Dec;21(12):1914-24. doi: 10.1038/cdd.2014.117. Epub 2014 Aug 15.

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

Author information

1
1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon 21079, France [2] Centre Georges François Leclerc, Dijon 21000, France [3] Faculté de Médecine et de Pharmacie, Université de Bourgogne, Dijon 21000, France.
2
1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon 21079, France [2] Centre Georges François Leclerc, Dijon 21000, France.
3
1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon 21079, France [2] Faculté de Médecine et de Pharmacie, Université de Bourgogne, Dijon 21000, France.
4
Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon 21079, France.
5
Institut Franche-Comté Electronique, Mécanique, Thermique et Optique-Sciences et Technologies (FEMTO-ST), Département Micro Nano Sciences and Systèmes, Université de Franche Comté, Besançon 25044, France.

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, LXRβ 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 LXRβ, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXRβ, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis.

PMID:
25124554
PMCID:
PMC4227150
DOI:
10.1038/cdd.2014.117
[Indexed for MEDLINE]
Free PMC Article

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