NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway

Purpose - In prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-beta 1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-beta 1/SMAD signaling pathway. Methods - In this study, we used flow cytometry to isolate CD44+/CD133+/NANOG+ PCSCs from DU145 prostate cancer cells. Then we used short hairpin RNA to silence NANOG and observed the biological behavior and the TGF-beta 1/SMAD signal of PCSCs. Results - NANOG decreased PCSC proliferation, increased apoptosis, and blocked cell cycling at G0/G1. Furthermore, reduction in the TGF-beta 1, p15, and p-SMAD2 expression was observed. Conclusion - These findings suggest that NANOG positively regulates the growth of PCSCs through the TGF-beta 1/SMAD signaling pathway.