title: Aberrant O-GlcNAc-modified proteins expressed in primary colorectal cancer.
abstract: O-GlcNAcylation is a post-translational modification of serine and threonine residues which is dynamically regulated by 2 enzymes; O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that catalyze the addition and removal of a single N-acetylglucosamine (GlcNAc) molecule, respectively. This modification is thought to be a nutrient sensor in highly proliferating cells via the hexosamine biosynthesis pathway, a minor branch of glycolysis. Although emerging evidence suggests that O-GlcNAc modification is associated with many types of cancer, identification of O-GlcNAc-modified proteins and their role in cancer remain unexplored. In the present study, we demonstrated that O-GlcNAcylation is increased in primary colorectal cancer tissues, and that this augmentation is associated with an increased expression of OGT levels. Using 2-dimensional O-GlcNAc immunoblotting and LC-MS/MS analysis, 16 proteins were successfully identified and 8 proteins showed an increase in O-GlcNAcylation, including cytokeratin 18, heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1), hnRNP H, annexin A2, annexin A7, laminin-binding protein, α-tubulin and protein DJ-1. Among these identified proteins, annexin A2 was further confirmed to show overexpression of O-GlcNAc in all cancer samples. The results, therefore, indicate that aberrant O-GlcNAcylation of proteins is associated with colorectal cancer and that identification of O-GlcNAc-modified proteins may provide novel biomarkers of cancer.
authors.affiliation: Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok, Thailand.
authors.forename: Thanong
authors.initials: T
authors.lastname: Phueaouan
authors.forename: Parunya
authors.initials: P
authors.lastname: Chaiyawat
authors.forename: Pukkavadee
authors.initials: P
authors.lastname: Netsirisawan
authors.forename: Daranee
authors.initials: D
authors.lastname: Chokchaichamnankit
authors.forename: Phaibul
authors.initials: P
authors.lastname: Punyarit
authors.forename: Chantragan
authors.initials: C
authors.lastname: Srisomsap
authors.forename: Jisnuson
authors.initials: J
authors.lastname: Svasti
authors.forename: Voraratt
authors.initials: V
authors.lastname: Champattanachai
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000302:isolation & purification* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D053719:Tandem Mass Spectrometry; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D006595:Hexosamines; D009363:Neoplasm Proteins; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine