Rourou Xiao, Lixin You, Li Zhang, Xichen Guo, Ensong Guo, Faming Zhao, Bin Yang, Xi Li, Yu Fu, Funian Lu, Zizhuo Wang, Chen Liu, Wenju Peng, Wenting Li, Xiaohang Yang, Yingyu Dou, Jingbo Liu, Wei Wang, Tianyu Qin, Yaoyuan Cui, Xiaoxiao Zhang, Fuxia Li, Yang Jin, Qingping Zeng, Beibei Wang, Gordon B Mills, Gang Chen, Xia Sheng, Chaoyang Sun
Targeting the G2/M checkpoint mediator WEE1 has been explored as a novel treatment strategy in ovarian cancer, but mechanisms underlying its efficacy and resistance remains to be understood. Here, it is demonstrated that the WEE1 inhibitor AZD1775 induces endoplasmic reticulum stress and activates the protein kinase RNA-like ER kinase (PERK) and inositol-required enzyme 1α (IRE1α) branches of the unfolded protein response (UPR) in TP53 mutant (mtTP53) ovarian cancer models. This is facilitated through NF-κB mediated senescence-associated secretory phenotype...
July 2022: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)