Fig. 9.

Summary of the study. The hexosamine biosynthesis pathway (HBP) and transsulfuration pathway, two main pathways associated with GFPT2 in this study, were illustrated. HBP is closely associated with the central carbon metabolism. The underscored metabolites were measured in this study. We used 1,2-¹³C Glc, 1-¹³C Gln, and 5-¹³C Gln in the ¹³C tracing experiment to trace the carbon flux into UDP-GlcNAc. GFPT2 is the rate-limiting enzyme in the HBP and was upregulated in mesenchymal cells, especially in partial EMT. It affected the HBP flux, EMT program (e.g., VIM), cell growth, and cell invasion, and it was overexpressed in claudin-low breast cancer represented by the D492HER2 cell line. GFPT2 was regulated by oxidative stress (H₂O₂ and GSH) and signaling regulators (insulin and EGF, and GSK3-β). Knockdown of GFPT2 with siRNAs decreased the cystathionine level and SQOR RNA expression in the transsulfuration pathway.