Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization.
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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DOI：
10.18632/oncotarget.5791
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Rébé C
中科院分区：
文献类型：
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作者：
Courtaut F;Derangère V;Chevriaux A;Ladoire S;Cotte AK;Arnould L;Boidot R;Rialland M;Ghiringhelli F;Rébé C
越来越多的证据表明肝脏 X 受体 (LXR) 具有一定的抗癌特性。我们最近证明，LXR 配体通过 LXRβ 依赖性途径诱导结肠癌细胞焦亡。在本研究中，我们发现人类结肠癌细胞系呈现出 LXRβ 的差异细胞质定位。这种定位与 LXR 配体处理下的 caspase-1 激活和细胞死亡诱导相关。 LXRβ 与截短形式的 RXRα (t-RXRα) 的结合导致 LXRβ 被隔离在结肠癌细胞的细胞质中。此外，t-RXRα在正常结肠上皮细胞中不表达。这些细胞主要呈现 LXRβ 的核定位，并且对 LXR 配体的细胞毒性具有抵抗力。我们的结果表明，LXRβ 的主要细胞质定位（发生在结肠癌细胞中，但不发生在正常结肠上皮细胞中）允许 LXR 配体诱导细胞焦亡。这项研究强化了 LXRβ 可能成为癌症治疗中有希望的靶点的假设。
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.