WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERT(high) Prostate Cancer Stem Cells.

Abstract

Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here, we report that the hTERT(high) prostate cancer cells exhibit CSC properties, including a stem cell-associated gene expression signature, long-term tumor-propagating capacity and epithelial-to-mesenchymal transition. In promoting the self-renewal symmetric division of hTERT(high) prostate cancer cells, WNT3a dramatically decreased the ratio of hTERT(high) prostate cancer cells undergoing asymmetric division. Increased WNT/β-catenin signal activation was also detected in hTERT(high) prostate cancer cells. hTERT-mediated CSC properties were at least partially dependent on β-catenin. These findings provide novel cellular and molecular mechanisms for the self-renewal of CSC orchestrated by tumor microenvironmental stimuli and intracellular signals. Cancer Res; 77(9); 2534-47. ©2017 AACR.