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RESEARCH PRODUCT

Liver X Receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization

Angélique ChevriauxRomain BoidotSylvain LadoireSylvain LadoireFrançois GhiringhelliFrançois GhiringhelliFlavie CourtautFlavie CourtautValentin DerangèreValentin DerangèreMickaël RiallandMickaël RiallandLaurent ArnouldAlexia Karen CotteAlexia Karen CotteCédric Rébé

subject

LXRβCytoplasmmedicine.medical_specialtyHydrocarbons FluorinatedColonColorectal cancerCaspase 1BiologyLigandsCell Line03 medical and health sciences0302 clinical medicineCell Line TumorInternal medicineRXRαsubcellular localizationmedicineHumansIntestinal MucosaLiver X receptorCytotoxicityLiver X Receptors030304 developmental biologySulfonamides0303 health sciencesRetinoid X Receptor alphaRetinoid X receptor alphaCaspase 1PyroptosisEpithelial CellsHCT116 CellsOrphan Nuclear ReceptorsSubcellular localizationmedicine.disease3. Good healthEnzyme ActivationGene Expression Regulation NeoplasticEndocrinologycolon cancerOncologyCell culture030220 oncology & carcinogenesisColonic NeoplasmsCancer researchPriority Research Paper

description

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.

yearjournalcountryeditionlanguage
2015-09-22Oncotarget
https://doi.org/10.18632/oncotarget.5791