Citation
- Authors: Derangere, V., Chevriaux, A., Courtaut, F., Bruchard, M., Berger, H., Chalmin, F., Causse, S. Z., Limagne, E., Vegran, F., Ladoire, S., Simon, B., Boireau, W., Hichami, A., Apetoh, L., Mignot, G., Ghiringhelli, F., Rebe, C.
- Year: 2014
- Journal: Cell Death Differ 21 1914-24
- Applications: in vitro / DNA, siRNA / INTERFERin, jetPRIME
- Cell types:
- Name: HCT 116
Description: Human colon carcinoma cells
Known as: HCT116 - Name: HEK-293T
Description: Human embryonic kidney Fibroblast
Known as: HEK293T, 293T
- Name: HCT 116
Method
INTERFERin (1 nM siRNA): HCT116jetPRIME: HEK-293T
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 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.