학술논문

Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells.
Document Type
Article
Source
Cell Death & Differentiation. Dec2014, Vol. 21 Issue 12, p1914-1924. 11p. 1 Diagram, 7 Graphs.
Subject
*GENETICS of colon cancer
*CANCER cell proteins
*ANTINEOPLASTIC agents
*CELL death inhibition
*CASPASES regulation
Language
ISSN
1350-9047
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]