GCN2通过激活胃癌中的PI3K/AKT信号通路促进脂肪酸代谢。

GCN2 promotes fatty acid metabolism through the activation of PI3K/AKT signaling in gastric cancer.

作者信息

Sun Dong, Sun Xu, Wang Xiaofeng, Zhang Jiazi, Liu Liqing, Xie Jiaping

机构信息

Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, Shandong, China; Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

出版信息

Cell Signal. 2025 Nov;135:111984. doi: 10.1016/j.cellsig.2025.111984. Epub 2025 Jul 10.

DOI:10.1016/j.cellsig.2025.111984

PMID:40651685

Abstract

PURPOSE

Our purpose was to investigate the impact and molecular mechanisms of GCN2 on gastric cancer.

METHODS

GCN2 expressions were measured in gastric cancer cells and tissues via qRT-PCR, western blot and immunohistochemistry staining. Cell functional assays were performed to elucidate the role of GCN2 in cell proliferation, apoptosis, migration, and invasion. BODIPY 493/503 staining was employed to assess the change of lipid droplets induced by GCN2. Additionally, the proteins expression was examined by western blot. Additionally, mice tumor xenograft models were also developed for in vivo analysis.

RESULTS

GCN2 was overexpressed in gastric cancer. GCN2 facilitated malignant behaviors of gastric cancer cells. Furthermore, GCN2 was found to facilitate the fatty acid metabolism in gastric cancer cells. Moreover, PI3K/Akt/mTOR signaling was activated by GCN2. Besides, rescue experiments results manifested that 740YP could attenuated the impact of GCN2 on the malignant behaviors and fatty acid metabolism of gastric cancer cells. Xenograft tumor models further demonstrated that GCN2 knockdown inhibited the growth of gastric cancer tumors by suppressing PI3K/AKT/mTOR signaling pathway.

CONCLUSION

This study provided evidences that GCN2 could promote fatty acid metabolism and tumor progression through the activation of PI3K/AKT/mTOR signaling in gastric cancer.

摘要

目的

我们的目的是研究GCN2对胃癌的影响及其分子机制。

方法

通过qRT-PCR、蛋白质印迹法和免疫组织化学染色检测胃癌细胞和组织中GCN2的表达。进行细胞功能实验以阐明GCN2在细胞增殖、凋亡、迁移和侵袭中的作用。采用BODIPY 493/503染色评估GCN2诱导的脂滴变化。此外，通过蛋白质印迹法检测蛋白质表达。另外，还建立了小鼠肿瘤异种移植模型用于体内分析。

结果

GCN2在胃癌中过表达。GCN2促进胃癌细胞的恶性行为。此外，发现GCN2促进胃癌细胞的脂肪酸代谢。而且，GCN2激活PI3K/Akt/mTOR信号通路。此外，挽救实验结果表明740YP可减弱GCN2对胃癌细胞恶性行为和脂肪酸代谢的影响。异种移植肿瘤模型进一步证明，敲低GCN2可通过抑制PI3K/AKT/mTOR信号通路抑制胃癌肿瘤的生长。