It is well known that post-translational modification of proteins is essential to control and regulate cell processes, the most common of which are glycosylation and phosphorylation. The two forms compete and coordinate with each other to form a continuous dynamic balance. When the balance is destroyed, the body will have corresponding symptoms, and cancer is one of the most obvious diseases. Phosphorylation and glycosylation generally compete for the same protein site, but there are two conditions that can be based on the synergy of residues.[1] Cancer cells can obtain a large amount of nutrients and substances from the surrounding environment through glycolysis to meet the needs of cell proliferation. This phenomenon is called Warburg effect.[2]Another important metabolic pathway of cancer cells is hexosamine biosynthesis pathway (HBP). Its final product, glucosamine diphosphate N-acetylglucosamine (UDP-GlcNAc), is the donor substrate of O-GlcNAcylation.

Researchers found that the overexpression of oncogene RAS could promote glycolysis and HBP levels, and indirectly stimulate O-GlcNAcylation. As a response to oncogene activation, the flux of cancer cells through HBP increases. In the transgenic model, oncogenic RAS increased its flux through glycolysis and HBP, resulting in an increase in O-GlcNAcylation. Interestingly, these RAS-driven tumors need GFAT expression to grow in vitro and in vivo. In addition, hypoxic cancer cells have been shown to contain high levels of HBP genes, including Gfpt1 and Gfpt2 and total O-GlcNAcylation, and the inhibition of HBP rate-limiting enzyme prevents the survival of cancer cells under hypoxic conditions [3].