Zeb1 promotes androgen independence of prostate cancer via induction of stem cell-like properties.

Current androgen deprivation therapy often leads to androgen independence. However, mechanism of the therapeutic failure is still not well understood. Here, we demonstrate elevated expression of Zeb1 in androgen-independent prostate cancer cells and prostate tumors of castrated PTEN conditional knockout mice. While Zeb1 shRNA resulted in a sensitization of androgen-independent prostate cancer cells, forced Zeb1 expression caused androgen-dependent prostate cancer cells to be more resistant to androgen deprivation. Moreover, such effects appeared to be mediated by induction of pluripotent genes or stem cell-like properties. Collectively, these findings suggest that inhibition of Zeb1 might be a potential therapeutic strategy for treatment of androgen-independent prostate cancer.