Galectin-7 promotes cisplatin efficacy by facilitating apoptosis and G3BP1 degradation in cervical cancer

半乳糖凝集素-7通过促进宫颈癌细胞凋亡和G3BP1降解来增强顺铂疗效

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作者:Chenglong Liu, Limin Zhou, Jia Chen, Zelan Yang, Shan Chen, Xueqing Wang, Xiaomei Liu, Yang Li, Can Zhang, Yirong Wang, Yihao Chen, Huan Li, Chao Shen, Hui Sun

Abstract

The emergence of chemoresistance in cervical cancer is extremely challenging in chemotherapy. Oxidative stress has emerged as the regulatory factor in drug resistance, but the detailed mechanism is still unknown. Stress granules, are membrane-less ribonucleoprotein-based condensates, could enhance chemoresistance by sequestering proapoptotic proteins inhibition of cell death upon exposure to drug-induced oxidative stress. Galectin-7, a member of galectin family, exerts varied roles in tumor repression or progression in different cancers. However, its role in cervical cancer has not been sufficiently studied. Here, we found that galectin-7 promotes cisplatin (CDDP) induced apoptosis and associates with stress granule-nucleating protein G3BP1 degradation. With the treatment of cisplatin, galectin-7 could enhance apoptosis by upregulating cleaved-PARP1 and the generation of reactive oxygen species (ROS), promoting mitochondrial fission, and reducing mitochondrial membrane potential (MMP). Furthermore, galectin-7 also reduces resistance by facilitating cisplatin-induced stress granules clearance through galectin-7/RACK1/G3BP1 axis. All these data suggested that galectin-7 promotes cisplatin sensitivity, and it would be potential target for potentiating efficacy in cervical cancer chemotherapy.

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