Open AccessLiver X receptor activation reduces gastric cancer cell proliferation by suppressing Wnt signalling via LXR β relocalization
Author(s) -
Wang Qiang,
Feng Fan,
Wang Jiayou,
Ren Meijia,
Shi Zhonggang,
Mao Xiang,
Zhang Heng,
Ju Xiaoli
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13974
Subject(s) - liver x receptor , wnt signaling pathway , agonist , cell growth , nuclear receptor , biology , microbiology and biotechnology , cancer research , receptor , signal transduction , chemistry , transcription factor , biochemistry , gene
Liver X receptors ( LXR s) are involved in various diseases associated with lipid disorders, and in regulating cancer cell proliferation. However, the underlying molecular mechanisms, especially those in gastric cancer ( GC ) remain to be clarified. In this study, immunohistochemistry analysis revealed that LXR β was mainly expressed in GC tissue, with less expression in adjacent normal tissues. The LXR β agonist T0901317 efficiently suppressed the proliferation and colony formation of various GC cell lines. We further showed that LXR β translocated from the cytoplasm to the nucleus when activated by T0901317. LXR β nuclear localization suppressed the activation of Wnt signalling and decreased the expression of target genes such as MYC , BMP 4, and MMP 7 through binding to their promoters. Moreover, we demonstrated that the LXR agonist efficiently suppressed GC tumour growth in a nude mouse xenograft model. Taken together, these results revealed that LXR β agonist inhibited GC cells proliferation by suppressing Wnt signalling via LXR β relocalization. The results strongly suggest that LXR β could be a promising target in GC therapy.