RXRα provokes tumor suppression through p53/p21/p16 and PI3K-AKT signaling pathways during stem cell differentiation and in cancer cells

Cell Death & Disease
Rui ZhangWenjian Ma

Abstract

The retinoid X receptor alpha (RXRα) is an important therapeutic target impacting diverse biological processes. Activation of RXRα is known to suppress cancer cell growth. However, the cellular mechanism has been elusive. In the present study, we addressed its role during stem cell differentiation and the underlying connections with carcinogenesis. RXRα was significantly upregulated following the differentiation of human mesenchymal stem cell (hMSC) toward the formation of endothelial cell (EC). However, overexpression of RXRα in hMSC provoked a senescence-like phenotype accompanied by the elevation of tumor suppressor p53, p21, and p16. Consistently, RXRα level was suppressed in cancer cells (~five times lower compared to differentiated hMSC), and its elevation could inhibit the proliferation, migration, and angiogenesis of cancer cells. We further demonstrated that these inhibitory effects were related to RXRα's interaction with estrogen receptor α (ERα) as well as EGF and ANGPTL3 through modulating PI3K/AKT signaling pathway by AKT and FAK phosphorylation. Moreover, RXRα inhibited glycolytic metabolism in cancer cells, which might be underlying its inhibition of differentiation and carcinogenic features. These data suggest t...Continue Reading

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Citations

Jan 8, 2019·Journal of Drug Targeting·Shuang JiangLi Qin
Jan 4, 2021·Breast Cancer Research and Treatment·Zhifa ZhangXiaofeng Dai
Jul 20, 2021·ACS Biomaterials Science & Engineering·Sung-Min KangShuichi Takayama
Jul 10, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Yan-Hong GuTing Zhang

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Methods Mentioned

BETA
transfection
co-immunoprecipitation assay
histone acetylation
flow cytometry
Infrared Imaging
Assay

Software Mentioned

image
Pro Plus

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