LXRα Promotes the Differentiation of Human Gastric Cancer Cells through Inactivation of Wnt/β-catenin Signaling

LXR alpha is a subtype of the liver X receptors (LXRs). There is accumulating evidence to support the involvement of LXR alpha in a variety of malignancies. However, the function and specific mechanism of LXRa in gastric cancer (GC) remain unclear. In this study, the expression of LXR alpha was significantly lower in poorly differentiated and undifferentiated GC tissues compared with well-and moderately differentiated GC tissues by immunohistochemistry analysis. The activation of LXR alpha leads to the decreased expression of beta-catenin, CD44, and Cyclin D1, whereas the inhibition of LXR alpha has opposite effect. The same results were obtained in animal experiments. Furthermore, results showed that CD44 and Cyclin D1 expression significantly decreased when Wnt/beta-catenin signaling was blocked in LXR alpha silent GC cells, whereas it was significantly increased when Wnt/beta-catenin signaling was activated in LXR alpha over-expressed GC cells. CD44 and Cyclin D1, downstream targets of Wnt/beta-catenin signaling, are specific markers for cell differentiation. Therefore, we conclude that LXR alpha may promote the differentiation of human GC cells through inactivation of Wnt/beta-catenin signaling.