title: Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization.
abstract: Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXRβ-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXRβ. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXRβ with the truncated form of RXRα (t-RXRα) was responsible for the sequestration of LXRβ in the cytoplasm in colon cancer cells. Moreover t-RXRα was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXRβ and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXRβ, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXRβ could be a promising target in cancer therapy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|UFR des Sciences de Santé, Université de Bourgogne, Dijon, France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Courtaut
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|UFR des Sciences de Santé, Université de Bourgogne, Dijon, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Derangère
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|Centre Georges François Leclerc, Dijon, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Chevriaux
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|UFR des Sciences de Santé, Université de Bourgogne, Dijon, France.|Centre Georges François Leclerc, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|UFR des Sciences de Santé, Université de Bourgogne, Dijon, France.
authors.forename: Alexia K
authors.initials: AK
authors.lastname: Cotte
authors.affiliation: Centre Georges François Leclerc, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnould
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|Centre Georges François Leclerc, Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|Faculté des Sciences, Université de Bourgogne, Dijon, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Rialland
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|UFR des Sciences de Santé, Université de Bourgogne, Dijon, France.|Centre Georges François Leclerc, Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France.|Centre Georges François Leclerc, Dijon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Rébé
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003106:Colon / Q000166:cytology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D020170:Caspase 1; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047490:Retinoid X Receptor alpha; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: LXRβ; RXRα; colon cancer; epithelial cells; subcellular localization