Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin

Pathol Res Pract. 2019 Dec;215(12):152681. doi: 10.1016/j.prp.2019.152681. Epub 2019 Oct 3.


The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions. Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme. Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC. The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients. Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells. The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT). These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.

Keywords: EMT; GFPT2; Serous ovarian cancer; β-catenin.

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Line, Tumor
  • Cell Movement
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Nucleus / pathology
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / genetics
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / metabolism*
  • Glycosylation
  • Hexosamines / biosynthesis*
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasms, Cystic, Mucinous, and Serous / enzymology*
  • Neoplasms, Cystic, Mucinous, and Serous / genetics
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Signal Transduction
  • beta Catenin / metabolism*


  • CTNNB1 protein, human
  • Hexosamines
  • beta Catenin
  • GFPT2 protein, human
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)