Sox5 Promotes Epithelial Mesenchymal Transition And Contributes To Prostate Cancer Metastasis

Prostate cancer(PCa) has been the most prevalent urology tumor in China, the strategy of PCa treatment including surgery, radiation therapy, immunotherapy, chemotherapy and hormone therapy, while hormone therapy is extensive applied in clinical, another way to understand hormone therapy is androgen deprivation treatment(ADT), the common drugs prescribed in clinical are Bicalutamide, MDV3100, abiraterone acetate etc. Despite the new drugs to deter the function of AR, patients develops into castration resistance prostate cancer inevitably in 1 or 2 years. What’s more, most patients diagnose PCa accompany with bone or lymph node metastases, which often bring about bone pain, pathologic fracture or other complications affect the quality of life. Thus it is of vital importance to thorough investigate the mechanism of the CRPC formation and prostate cancer metastases, these can bring about hopeful therapeutic way to manage PCa.It has been point out that Sox5 promotes the proliferation and metastases in hepatoma and pituitary tumor. We detect the expression of Sox5 in prostate cancer tissue by immunohistochemistry, patients with high Sox5 expression are more likely to suffer from metastases, these patients often express high level mesenchymal marker. The PCa lymph nodes metastases tissue is also detected high Sox5 expression. Knock down Sox5 in prostate cancer cellline PC3 and 22Rv1 decrease the ability of migration, also down regulates the mesenchymal marker, suggests Sox5 promote epithelial mesenchymal transition. Utilize 22Rv1 xenotransplantation model to explore the function of Sox5 in metastases. We find that knock down Sox5 in the xenografts can reduce the proliferation and metastases of PCa.When treat the LNCaP cells with TGF-β, the cells became more mesenchymal phenotype with the expression of Sox5 increase. Knock down Sox5 in LNCaP can reverse the mesenchymal induction by TGF-β. The JASPAR software indicate that Smad3 can binds to the promotor of Sox5, Chip-PCR and Luciferase assay verify the prediction, papers and JASPAR indicated that Sox5 regulate TWIST1 to promote EMT, knock down Sox5 lead to TWIST1 downregulate, suggest Sox5 regulate TWIST1 to promote epithelial mesenchymal transition. To investigate the process of CRPC, we culture LNCaP cell with charcoal dextran fetal bovine serum, the cell viability decreased at first and recover accompany with Sox5 expression increase, the recovery cell so called CR-LN, CR-LN also express more mesenchymal marker than parental. Knock down Sox5 in CR-LN decrease the cell viability as well the mesenchymal marker. Migration assay indicated that knock down Sox5 lead to migratory ability decrease, also colony formation assay suggest cell self renew ability decrease.Together, in the ADT process, Sox5 get rid of AR inhibition, the expression of Sox5 increase. As a result of Sox5 expression increase, cancer cells proliferation escape from the ADT, and cell motility increased, cancer would facility for metastasis. Thus the Sox5 or its downstream may be a promising target for PCa therapy.