标题：PBK, targeted by EVI1, promotes metastasis and confers cisplatin resistance through inducing autophagy in high-grade serous ovarian carcinoma
作者：Ma, Hanlin; Li, Yingwei; Wang, Xiangxiang; Wu, Huan; Qi, Gonghua; Li, Rongrong; Yang, Ning; Gao, Min; Yan, Shi; Yuan, Cunzhong; Ko 更多 作者机构：[Ma, Hanlin; Li, Yingwei; Wang, Xiangxiang; Wu, Huan; Qi, Gonghua; Li, Rongrong; Yang, Ning; Gao, Min; Yan, Shi; Yuan, Cunzhong; Kong, Beihua] Shandon 更多
通讯作者：Kong, BH;Kong, BH
通讯作者地址：[Kong, BH]Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Shandong, Peoples R China;[Kong, BH]Shandong Univ, Qilu Hosp, Gynecol Oncol K 更多
来源：CELL DEATH & DISEASE
摘要：High-grade serous ovarian carcinoma (HGSOC) is the most lethal type of gynecologic malignancy. Chemoresistance is the main reason for the poor prognosis of HGSOC. PDZ-binding kinase (PBK) promotes the malignant progression of various carcinomas. However, the roles and clinical significance of PBK in HGSOC remain unclear. Here, we reported that PBK was overexpressed in HGSOC tissues and cell lines. High PBK expression was associated with a poor prognosis, metastasis, and cisplatin resistance of HGSOC. Overexpression of PBK promoted autophagy and enhanced cisplatin resistance via the ERK/mTOR signaling pathway. Further study showed that inhibition of autophagy by chloroquine or bafilomycin A1 reversed PBK-induced cisplatin resistance. Overexpression of PBK decreased ovarian cancer responsiveness to cisplatin treatment through inducing autophagy in vivo. We also demonstrated that the PBK inhibitor OTS514 augmented the growth inhibition effect of cisplatin in vitro and in vivo. Moreover, ecotropic viral integration site-1 (EVI1) could regulate PBK expression through directly targeting the PBK promoter region. In conclusion, high PBK expression was correlated with a poor prognosis, metastasis, and cisplatin resistance through promoting autophagy in HGSOC. PBK might be a promising target for the early diagnosis and individual treatment of ovarian cancer.