2025/01/01 by Gay Pauline Padilla‐Meier, Yeshika Bhatia, Suresh Mishra · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Immunology and Microbiology · #Glycosylation and Glycoproteins Research #Carbohydrate Chemistry and Synthesis #Galectins and Cancer Biology
paper · doi:10.1139/bcb-2025-0055
openalex publication_date 2025/01/01 · openalex created_date 2025/05/15 · openalex updated_date 2026/07/02
The hexosamine biosynthetic pathway (HBP) is upregulated in many cancer cell types leading to upregulation of post-translational modification of proteins by β- N-acetylglucosamine ( O-GlcNAc), the product of HBP. However, our knowledge of the identity of proteins that undergo O-GlcNAcylation in cancer cells and consequently their roles is very limited. We investigated the O-GlcNAcylation of epidermal growth factor receptor (EGFR) and glucose transporter 1 (GLUT1) in T47D and MDA-MB-231 breast cancer cell models. We examined the effect of the loss of putative O-GlcNAcylation sites in EGFR and GLUT1 on cell-signaling pathways and their functional consequences on cell cycle progression and cell metabolism using fluorescence-activated cell sorting analysis and in vitro assays. EGFR and GLUT1 undergo O-GlcNAcylation in T47D and MDA-MB-231 breast cancer cells, which enhances their functions and prevents their intrinsic downregulation. This appears to involve an interplay between phosphorylation, O-GlcNAcylation, and ubiquitination in both proteins. Importantly, perturbing the putative O-GlcNAcylation sites in both proteins adversely affected their stability, functions, and metabolic status of breast cancer cells, including glucose uptake and lactate production. In conclusion, the reprogrammed metabolism in cancer cells extends beyond energy and macromolecule requirements and contributes to cell-signaling events that support the stability and function of cancer promoting proteins.