Metformin promotes cGAS/STING signaling pathway activation by blocking AKT phosphorylation in gastric cancer

被引：11

作者：

Shen, Qian ^{[1
]}

Yang, Lei ^{[1
]}

Li, Chengguo ^{[1
]}

Wang, Tao ^{[1
]}

Lv, Jianbo ^{[1
]}

Liu, Weizhen ^{[1
]}

Lin, Yao ^{[1
]}

Yin, Yuping ^{[1
]}

Tao, Kaixiong ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastrointestinal Surg, Wuhan, Peoples R China

来源：

HELIYON | 2023年 / 9卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Gastric cancer; Metformin; cGAS/STING; AKT; SOX2; AMPK;

D O I：

10.1016/j.heliyon.2023.e18954

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The cGAS/STING signaling pathway plays a pivotal role in regulating innate immunity. Emerging novel drugs aim to regulate the anti-tumor immune response by activating innate immunity. The anti-diabetic drug metformin has been reported to exhibit anti-cancer effect against various types of cancer. However, the role of metformin in regulating the cGAS/STING signaling pathway in gastric cancer remains unknown. In our study, we first used bioinformatic analysis to detect that metformin is closely related to tumor immunity in multiple tumors. Next, we validated the function of metformin in activating the cGAS/STING signaling pathway in gastric cancer cell lines. In addition, KEGG pathway enrichment analysis showed that metformin is negatively correlated with the PI3K/AKT signaling pathway in gastric cancer. We further verified that metformin activates the cGAS/STING signaling pathway by blocking AKT phosphorylation. Moreover, we found that metformin regulates the AKT signaling pathway by mediating the transcription factor SOX2. Thus, our study indicates that metformin activates the cGAS/STING signaling pathway by suppressing SOX2/AKT and has promising potential in gastric cancer immunotherapy.

引用

页数：11

共 36 条

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