Open AccessRetinoid X receptor α enhances human cholangiocarcinoma growth through simultaneous activation of Wnt/β‐catenin and nuclear factor‐κB pathways
Author(s) -
Huang GuiLi,
Zhang Wei,
Ren HongYue,
Shen XueYing,
Chen QingXi,
Shen DongYan
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12802
Subject(s) - cyclin d1 , wnt signaling pathway , retinoid x receptor , downregulation and upregulation , cancer research , biology , nuclear receptor , retinoid , retinoid x receptor alpha , cell growth , catenin , microbiology and biotechnology , cell cycle , chemistry , signal transduction , cell , transcription factor , cell culture , retinoic acid , biochemistry , genetics , gene
Retinoid X receptor α ( RXR α) plays important roles in the malignancy of several cancers such as human prostate tumor, breast cancer, and thyroid tumor. However, its exact functions and molecular mechanisms in cholangiocarcinoma ( CCA ), a chemoresistant carcinoma with poor prognosis, remain unclear. In this study we found that RXR α was frequently overexpressed in human CCA tissues and CCA cell lines. Downregulation of RXR α led to decreased expression of mitosis‐promoting factors including cyclin D1and cyclin E, and the proliferating cell nuclear antigen, as well as increased expression of cell cycle inhibitor p21, resulting in inhibition of CCA cell proliferation. Furthermore, RXR α knockdown attenuated the expression of cyclin D1 through suppression of Wnt/β‐catenin signaling. Retinoid X receptor α upregulated proliferating cell nuclear antigen expression through nuclear factor‐κB ( NF ‐κB) pathways, paralleled with downregulation of p21. Thus, the Wnt/β‐catenin and NF ‐κB pathways account for the inhibition of CCA cell growth induced by RXR α downregulation. Retinoid X receptor α plays an important role in proliferation of CCA through simultaneous activation of Wnt/β‐catenin and NF ‐κB pathways, indicating that RXR α might serve as a potential molecular target for CCA treatment.