Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein

顺铂诱导的自噬通过调节 yes 相关蛋白保护乳腺癌细胞免于凋亡

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作者:Yulin Jiang, Feihu Ji, Yifeng Liu, Mengjia He, Zhiqian Zhang, Junhong Yang, Nian Wang, Changli Zhong, Qianni Jin, Xiangsen Ye, Tingmei Chen

Abstract

Breast cancer is a common cause of cancer‑related deaths in women. Treatment with cisplatin exhibits some therapeutic efficacy. However, treatment optimization is required, and the mechanisms underlying the cisplatin's proapoptotic effects remain unclear. In the present study, we demonstrated that cisplatin induced apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin played a protective role in breast cancer cells, which impaired its proapoptotic effect. Mechanistically, for the first time, we found that cisplatin treatment activated the MAPK signaling pathway and promoted autophagy via the ERK signaling pathway. Notably, we found that nuclear translocation of yes-associated protein (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a survival input that promoted survival in cisplatin-treated breast cancer cells. These findings revealed that administration of cisplatin along with an autophagy inhibitor is a promising therapeutic strategy for treating breast cancer.

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