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

• DOI: 10.1038/s41419-018-0610-1
• Publication Date: 2018-05-10T08:38:41Z
• Authors: Rui Zhang; Hui Li; Shuangshuang Zhang; Yujie Zhang; Nan Wang; Hao Zhou; Hongpeng He; Guang Hu; Tong-Cun Zhang; Wenjian Ma
• Keywords: Retinoid X receptor

Abstract The retinoid X receptor alpha (RXRα) is an important therapeutic target impacting diverse biological processes. Activation of RXRα known to suppress cancer cell growth. However, the cellular mechanism has been elusive. In present study, we addressed its role during stem differentiation and underlying connections with carcinogenesis. was significantly upregulated following human mesenchymal (hMSC) toward formation endothelial (EC). overexpression in hMSC provoked a senescence-like phenotype accompanied by elevation tumor suppressor p53, p21, p16. Consistently, level suppressed cells (~five times lower compared differentiated hMSC), could inhibit proliferation, migration, angiogenesis cells. We further demonstrated that these inhibitory effects were related RXRα’s interaction estrogen α (ERα) as well EGF ANGPTL3 through modulating PI3K/AKT signaling pathway AKT FAK phosphorylation. Moreover, inhibited glycolytic metabolism cells, which might be inhibition carcinogenic features. These data suggest acts rather than driving force differentiation, unbalanced can trigger multiple yet connected pathways preventing