Paclitaxel is a main ingredient in the
combination chemotherapy treatment of advanced human cervical
squamous cell carcinomas. We investigated the roles and underlying molecular mechanisms of PinX1 in cervical
squamous cell carcinomas (CSCC) cells response to
paclitaxel and its clinical significances. The expression dynamics of PinX1 was first examined by immunohistochemistry in 122 advanced CSCC patients treated with
cisplatin/
paclitaxel chemotherapy. The expression of PinX1 was significantly associated with the effects of
cisplatin/
paclitaxel chemotherapy in advanced CSCCs (P<0.05). High expression of PinX1 correlated with CSCC's response to
cisplatin/
paclitaxel chemotherapy, and was an independent predictor of shortened survival (P<0.05). A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on CSCC cells chemosensitivity to
paclitaxel and underlying mechanisms. In CSCC cells, the levels of PinX1 were only associated with the cytotoxicity and sensitivity of
paclitaxel, in which knockdown of PinX1 dramatically enhanced
paclitaxel cytotoxicity, whereas the reestablishment of PinX1 levels substantially reduced the
paclitaxel-induced killing effect. In addition, we identified that the ability of PinX1 to stabilize the tension between sister kinetochores and maintain the spindle assembly checkpoint was the main reason CSCC cells undergo apoptosis when treated with
paclitaxel, and further studies demonstrated that shortened distance between sisters kinetochores by
nocodazole confers upon PinX1-replenished cells a sensitivity to the death inducing
paclitaxel effects. Furthermore, our study of CSCC cells xenografts in nude mice confirmed the role of PinX1 in
paclitaxel sensitivity in vivo. Our data reveal that PinX1 could be used as a novel predictor for CSCC patient response to
paclitaxel, and the role of PinX1-mediated
paclitaxel sensitivity might represent a new direction for the development of a new generation of microtubule drugs.