Roles of NANOGP8 in cancer metastasis and cancer stem cell invasion during development of castration-resistant prostate cancer.

Abstract

BackgroundProstate cancer (PCa) is one of the most common types of cancer and the emerging resistance to androgen deprivation therapy in PCa aggravates disease progression. In this study, we examined the potential pro-tumorigenic functions of NANOGP8 in prostate cancer development.MethodsQuantitative RT-PCR confirmed higher NANOGP8 expression in androgen independent tumors, as well as a recurrent prostate tumor in patient samples. We then established a novel two-way inducible NANOGP8-short hairpin RNA experimental system, in which the NANOGP8 expression was transiently induced by adding doxycycline in the diet of NOD/SCID mice.ResultsThe knockdown of NANOGP8 inhibited implanted tumor growth and the progression of castration-resistant PCa. NANOGP8-deficient PCa cells lost their cancer stem cell and gene expression programs. To further investigate the functions of NANOGP8 in PCa stem cells, real-time cell tracking was used to monitor the cell division modes and differentiation patterns of NANOGP8+ cells. The expression level of NANOGP8 markedly influenced the cell division mode of NANOGP8+ PCa cells and was strongly correlated with their pluripotency, reflected by robust telomerase activity and longer telomere length. NANOGP8 expression was also associated with the metastatic capacity of PCa cells.ConclusionsBased on these findings, we propose that NANOGP8 could serve as an effective therapeutic target for the treatment of PCa.