Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response

Nan Lin; Liankun Sun; Jiannan Chai; Hang Qi; Yuanxin Zhao; Jiaoyan Ma; Meihui Xia; Xiaoqing Hu

doi:10.1186/s12935-024-03210-x

Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response

Cancer Cell Int. 2024 Jan 18;24(1):38. doi: 10.1186/s12935-024-03210-x.

Authors

Nan Lin^{1

2}, Liankun Sun², Jiannan Chai³, Hang Qi², Yuanxin Zhao², Jiaoyan Ma², Meihui Xia⁴, Xiaoqing Hu⁵

Affiliations

¹ First Hospital of Jilin University, Changchun, China.
² Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
³ Department of Clinical Laboratory, First Hospital of Jilin University, Changchun, 130021, China.
⁴ Department of Obstetrics, First Hospital of Jilin University, Changchun, 130021, China.
⁵ Department of Ophthalmology, First Hospital of Jilin University, 130021, Changchun, China. huxq@jlu.edu.cn.

Abstract

Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the mitochondrial unfolded protein response (UPR^mt) in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, which may provide a new insight into the mechanisms of antitumor drug functions.

Abstract

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