Docetaxel-based chemotherapy confers higher five-year survival rate for patients with castration-resistant prostate cancer (CRPC). However, docetaxel-resistant prostate cancers are more malignant related to poor prognosis. We determine the cause of the aggressive phenotype of docetaxel-resistant prostate cancer (PCa). In our study, the docetaxel-resistant CRPC- PC/DX25 cells exhibit higher mobility and express more endogenous CD44. CD44 is a multifunctional protein involved in regulation of drug resistance and cell migration. CD44 has been reported to function as upstream regulator of Yes-associated protein (YAP), a major mediator in Hippo-pathway which is involved in human tumorigenesis. Knockdown of CD44 reduces protein expression of YAP but increases protein level of phospho-YAP S127. Phosphorylation of S127 on YAP suppresses the oncogenic activity of YAP as well as decreases protein expression of CTGF and CYR61, the downstream genes of YAP. CTGF and CYR61 are related to cell migration, cell invasion, and cell adhesion. In conclusion, CD44/YAP pathway may be a potential therapeutic target for docetaxel-resistant CRPCs.
