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

被引：148

作者：

Derangere, V. ^{[1
,2
,3
]}

Chevriaux, A. ^{[1
,2
]}

Courtaut, F. ^{[1
,3
]}

Bruchard, M. ^{[1
,3
]}

Berger, H. ^{[1
,3
]}

Chalmin, F. ^{[1
,3
]}

Causse, S. Z. ^{[1
]}

Limagne, E. ^{[1
,3
]}

Vegran, F. ^{[1
,3
]}

Ladoire, S. ^{[1
,2
,3
]}

Simon, B. ^{[4
]}

Boireau, W. ^{[4
]}

Hichami, A. ^{[1
,3
]}

Apetoh, L. ^{[1
,2
,3
]}

Mignot, G. ^{[1
]}

Ghiringhelli, F. ^{[1
,2
,3
]}

Rebe, C. ^{[1
,2
]}

机构：

[1] INSERM, UMR 866, F-21079 Dijon, France

[2] Ctr Georges Francois Leclerc, F-21000 Dijon, France

[3] Univ Bourgogne, Fac Med & Pharm, F-21000 Dijon, France

[4] Univ Franche Comte, Inst Franche Comte Elect Mecan Therm & Opt Sci &, Dept Micro Nano Sci & Syst, F-25044 Besancon, France

来源：

CELL DEATH AND DIFFERENTIATION | 2014年 / 21卷 / 12期

关键词：

LXR; DEATH; PROLIFERATION; PROGRESSION; INHIBITION; ANDROGEN; RELEASE; GROWTH; ROLES; ABCA1;

D O I：

10.1038/cdd.2014.117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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

引用

页码：1914 / 1924

页数：11

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