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Liver X Receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization
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Flavie Courtaut1,2,*, Valentin Derangère1,2,*, Angélique Chevriaux1,3, Sylvain Ladoire1,2,3, Alexia K. Cotte1,2, Laurent Arnould3, Romain Boidot1,3, Mickaël Rialland1,4, François Ghiringhelli1,2,3 and Cédric Rébé1,3
1 Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 866, Dijon, France
2 UFR des sciences de santé, Université de Bourgogne, Dijon, France
3 Centre Georges François Leclerc, Dijon, France
4 Faculté des sciences, Université de Bourgogne, Dijon, France
* These authors have contributed equally to this work
Cédric Rébé, email:
Keywords: LXRβ, RXRα, colon cancer, epithelial cells, subcellular localization
Received: June 16, 2015 Accepted: September 08, 2015 Published: September 22, 2015
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.
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