Aberrant O-GlcNAcylated Proteins: New Perspectives in Breast and Colorectal Cancer

Abstract

Increasing glucose consumption is thought to provide an evolutionary advantage to cancer cells. Alteration of glucose metabolism in cancer influences various important metabolic pathways including the hexosamine biosynthesis pathway (HBP), a relatively minor branch of glycolysis. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an end product of HBP, is a sugar substrate used for classical glycosylation and O-GlcNAcylation, a post-translational protein modification implicated in a wide range of effects on cellular functions. Emerging evidence reveals that certain cellular proteins are abnormally O-GlcNAc modified in many kinds of cancers, indicating O-GlcNAcylation is associated with malignancy. Since O-GlcNAc rapidly on and off modifies in a similar time scale as in phosphorylation and these modifications may occur on proteins at either on the same or adjacent sites, it suggests that both modifications can work to regulate the cellular signaling pathways. This review describes the metabolic shifts related to the HBP, which are commonly found in most cancers. It also describes O-GlcNAc modified proteins identified in primary breast and colorectal cancer, as well as in the related cancer cell lines. Moreover, we also discuss the potential use of aberrant O-GlcNAcylated proteins as novel biomarkers of cancer.

Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice

“…Studies have demonstrated that proteins involved in mRNA processing can be O-GlcNacylated which may regulate transcriptional activity 52 . Indeed, GR regulation of the transcriptional regulator NFκB has been shown to be at least partially mediated by the OGT/GR complex in vitro as evidenced by increased OGT induced O-GlcNAcylation and decreased phosphorylation of RNA polymerase II 26 .…”

O-Glcnac Glycosylation of Rad51 Plays an Important Role in Promoting Colorectal Cancer Cell Invasion

“…Common post-translational modifications of proteins include phosphorylation, ubiquitination, acetylation, glycosylation, methylation and SUMOylation, which are involved in the process of tumor cell cycle, proliferation, invasion, apoptosis, adhesion and immune defense, development [23]. O-GlcNAc Glycosylation is an important monosaccharidic modification of serine and threonine residues in mammalian intracellular proteins, which is associated with various diseases [12,24]. In recent years, the role of O-GlcNAc glycosylation has been widely recognized in tumor development and anti-tumor drugs resistance [25].…”

“…Notably, O-linked glycosylation (O-GlcNAc) glycosylation, as a posttranslational modification of functional proteins, has drawn more and more attentions in the process of tumor genesis and metastasis [11,12]. Meanwhile, the O-GlcNAc glycosylation will affect the interaction, stability and cell localization of oncoprotein/oncogenic proteins, and then regulate the tumor cells malignant biological behaviors [11].…”

Ultrafast and high-throughput N-glycan analysis for monoclonal antibodies

“…4,15,18 Relating to human diseases, abnormal glycan profiles have been implicated in human genetic disorders, 19,20 muscular dystrophies, 21 neurological diseases, 22 and cancers. [23][24][25][26] During novel therapeutic mAb development, glycosylation is considered a critical quality attribute that must be closely monitored, and it has attracted increasing attention from the regulatory agencies. 27 Glycans in mAbs represent an average of 2-3% of the total antibody mass, 2,4 and their expression and structure are influenced by cell culture process conditions.…”