Author's view: epithelial plasticity metabolically reprograms normal cells towards a neoplastic-prone state.

We have uncovered that epithelial plasticity programs metabolically reprogram epithelial lung cells by increasing expression of genes (e.g., glutamine-fructose-6-phosphate transaminase 2 - GFPT2 and UDP-N-acetylglucosamine pyrophosphorylase 1 - UAP1) critical for the hexosamine biosynthetic pathway (HBP) and elevating global protein O-GlcNAcylation - a specific type of glycosylation. We found that increased O-GlcNAcylation could suppress oncogene-induced senescence tumor suppressor pathways that ultimately led to accelerated KrasG12D -driven lung tumorigenesis.