The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5-fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway

Mol Carcinog. 2024 Apr;63(4):688-700. doi: 10.1002/mc.23681. Epub 2024 Jan 15.

Abstract

Gastric cancer (GC) is a prevalent malignancy of the digestive system. Distant metastasis and chemotherapy resistance are the crucial obstacles to prognosis in GC. Recent research has discovered that the glucose-6-phosphatase catalytic subunit (G6PC) plays an important role in tumor malignant development. However, little evidence has highlighted its role in GC. Herein, through a comprehensive analysis including profiling of tissue samples and functional validation in vivo and in vitro, we identify G6PC as a crucial factor in GC tumorigenesis. Importantly, we found that the FOXO1/G6PC axis could accelerate GC cell proliferation, metastasis, and 5-Fluorouracil (5-FU) resistance by targeting the PI3K/AKT/mTOR signaling pathway, implicating that as a prospective therapeutic approach in GC.

Keywords: 5-FU resistance; FOXO1; G6PC; Gastric cancer; PI3K/AKT/mTOR; Progression.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Stomach Neoplasms* / pathology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Fluorouracil
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • FOXO1 protein, human
  • Forkhead Box Protein O1