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

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

  • Cell Signal. 2025 Nov:135:111984. doi: 10.1016/j.cellsig.2025.111984.
Dong Sun 1,  Xu Sun 2,  Xiaofeng Wang 2,  Jiazi Zhang 2,  Liqing Liu 2,  Jiaping Xie 3
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 3 Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, Shandong, China; Department of Gastroenterology, The Fifth People's Hospital of Liaocheng, Liaocheng, Shandong, China. Electronic address: lcjiapingxie@126.com.
PMID: 40651685 DOI: 10.1016/j.cellsig.2025.111984
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.

Keywords

Fatty acid metabolism; GCN2; Gastric cancer; PI3K/AKT/mTOR pathway.

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