GFPT2, also known as Glutamine-Fructose-6-Phosphate Transaminase 2, is a key enzyme in the hexosamine biosynthesis pathway (HBP). HBP produces UDP-GlcNAc, which is used for protein O-GlcNAcylation. This pathway plays important roles in metabolism, health, and aging [4].

In pancreatic cancer, GFPT2 promotes macrophage M2 polarization and the malignant phenotype of cancer cells, and the GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment [1]. In KRAS mutant/p53 wild-type lung cancer, nutlin-3a-induced non-apoptotic methuosis-like cell death is dependent on GFPT2 [2]. In mesothelioma, GFPT2 shows high sensitivity in diagnosis, and its overexpression is linked to a poor prognosis as it drives malignant proliferation, invasiveness, and metastasis by activating the NF-κB signalling pathway [3]. In pancreatic cancer, gemcitabine administration induces GFPT2 expression, which enhances invasion by activating HBP [5]. In colorectal cancer, GFPT2 promotes metastasis and forms a positive feedback loop with p65 [6]. In colon cancer, GFPT2 is highly expressed, associated with poor prognosis, and correlated with the tumor microenvironment, including immunosuppressive cells [7]. In KRAS/LKB1 mutant lung cancer, GFPT2 is highly dependent on for growth, making it a potential target [8]. In breast cancer, GFPT2 is upregulated in epithelial-mesenchymal transition, controls cell growth and invasion, and is a marker for oxidative stress [9].

In conclusion, GFPT2, as a key enzyme in the HBP, is involved in multiple biological processes related to cancer. Studies, including those potentially involving KO/CKO mouse models (although not all abstracts specified model types), have shown its importance in tumor-related phenotypes such as metastasis, immune microenvironment regulation, and cell death in various cancers, providing potential therapeutic targets for these disease areas.