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

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 LXR beta-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXR beta. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXR beta with the truncated form of RXRa (t-RXRa) was responsible for the sequestration of LXR beta in the cytoplasm in colon cancer cells. Moreover t-RXRa was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXR beta and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXR beta, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXR beta could be a promising target in cancer therapy.