FTO Promotes the Stemness of Gastric Cancer Cells

DNA Cell Biol. 2023 Jul;42(7):411-420. doi: 10.1089/dna.2023.0074. Epub 2023 May 25.

Abstract

The full name of the FTO gene is fat mass and obesity-associated gene. In recent years, it has also been found that FTO is involved in m6A demethylation and regulates the progression of multiple cancers, including gastric cancer. The cancer stem cell theory argues that cancer stem cells are key factors in cancer metastasis, and inhibiting the expression of stemness genes is a good method to inhibit metastasis of gastric cancer. Currently, the role of the FTO gene in regulating stemness of gastric cancer cells is still unclear. By analyzing public databases, it was discovered that FTO gene expression was increased in gastric cancer, and high expression of FTO was associated with poor prognosis of patients with gastric cancer. After gastric cancer stem cells were isolated, it was found that FTO protein expression was increased in gastric cancer stem cells; stemness of gastric cancer cells was reduced after the FTO gene knockdown; subcutaneous tumors of nude mice were smaller than those of the control group after FTO knockdown; and stemness of gastric cancer cells was enhanced after FTO was overexpressed by plasmid. By reviewing additional literature and experimental validation, we found that SOX2 may be the factor by which FTO promotes the stemness of gastric cancer cells. Therefore, it was concluded that FTO could promote the stemness of gastric cancer cells, and targeting FTO may be a potential therapeutic approach for patients with metastatic gastric cancer. CTR number: TOP-IACUC-2021-0123.

Keywords: FTO; cancer; stemness.

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / metabolism
  • Animals
  • Cell Line, Tumor
  • Mice
  • Mice, Nude
  • Stomach Neoplasms* / pathology

Substances

  • FTO protein, mouse
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO