J Cancer 2019; 10(1):156-167. doi:10.7150/jca.28600

Research Paper

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

Yu Gao1, Zihua Chen1, Ran Wang2, Xiangzhou Tan1, Changhao Huang1, Guanyang Chen1, Zhikang Chen2✉

1. Department of Gastrointestinal Surgery, Xiangya Hospital of Central South University, Hunan key laboratory of precise diagnosis and treatment of gastrointestinal tumor, Changsha, Hunan, P.R. China;
2. Department of Colorectal and Anus Surgery, Xiangya Hospital of Central South University, Hunan key laboratory of precise diagnosis and treatment of gastrointestinal tumor, Changsha, Hunan, P.R. China.

Abstract

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

Keywords: liver X receptor alpha, stomach neoplasms, cell differentiation, Wnt beta-catenin signaling pathway, CD44 antigen

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How to cite this article:
Gao Y, Chen Z, Wang R, Tan X, Huang C, Chen G, Chen Z. LXRα Promotes the Differentiation of Human Gastric Cancer Cells through Inactivation of Wnt/β-catenin Signaling. J Cancer 2019; 10(1):156-167. doi:10.7150/jca.28600. Available from http://www.jcancer.org/v10p0156.htm