The overexpression of P21-activated kinase 5 (PAK5) promotes paclitaxel-chemoresistance of epithelial ovarian cancer

Abstract

P21-activated kinase 5 (PAK5) is the recently identified member of the group II p21-activated kinases (PAKs) family, which is characterized by a highly conserved amino-terminal Cdc42/Rac interactive binding domain and a carboxyl terminal kinase domain. However, the role of PAK5 in gynecological cancers has not been evaluated so far. It is remarkable that we found PAK5 was overexpressed in epithelial ovarian cancer (EOC), which is faced with an obstacle of paclitaxel resistance. Therefore, in this study, we aim to examine the PAK5 expression during EOC progression, the role of PAK5 in malignant progression of EOC and the probable relationship between PAK5 and EOC paclitaxel resistance. By immunohistochemistry, our results showed that PAK5 expression was increased with EOC progression through the adenoma to carcinoma sequence, with the highest expression level in invasive and metastatic EOCs. Furthermore, the expression level of PAK5 was also found to increase in accordance with the development of EOC Federation International of Gynecology and Obstetrics stages (P = 0.038) and differentiation grades (P = 0.008). Remarkably, those patients who recurred within 6 months after accepting tumor reductive surgery and the following carboplatin + paclitaxel chemotherapy had the highest PAK5 expression (P = 0.015). Moreover, in in vitro studies, we found that SK-OV-3 cell growth was decreased while paclitaxel chemosensitivity was correspondingly increased with the down-regulation of PAK5. Taken together, our study demonstrated that PAK5 is correlated to human EOC and increased PAK5 expression promotes EOC progression, and PAK5 regulates EOC cell paclitaxel chemoresistance.