1. Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells.
- Author
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Derangère, V, Chevriaux, A, Courtaut, F, Bruchard, M, Berger, H, Chalmin, F, Causse, S Z, Limagne, E, Végran, F, Ladoire, S, Simon, B, Boireau, W, Hichami, A, Apetoh, L, Mignot, G, Ghiringhelli, F, and Rébé, C
- Subjects
GENETICS of colon cancer ,CANCER cell proteins ,ANTINEOPLASTIC agents ,CELL death inhibition ,CASPASES regulation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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