title: Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells.
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.
authors.affiliation: 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.
authors.forename: V
authors.initials: V
authors.lastname: Derangère
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Chevriaux
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Courtaut
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Bruchard
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Berger
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Chalmin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon 21079, France.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Causse
authors.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: Limagne
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Végran
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: 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.
authors.forename: B
authors.initials: B
authors.lastname: Simon
authors.affiliation: 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.
authors.forename: W
authors.initials: W
authors.lastname: Boireau
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Hichami
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon 21079, France.
authors.forename: G
authors.initials: G
authors.lastname: Mignot
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Rébé
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008807:Mice, Inbred BALB C; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000255:Adenosine Triphosphate; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D020170:Caspase 1; D017630:Connexins; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009419:Nerve Tissue Proteins; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C453881:NLRP3 protein, human; C492764:PANX1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides