title: Enzymes for N-Glycan Branching and Their Genetic and Nongenetic Regulation in Cancer.
abstract: N-glycan, a fundamental and versatile protein modification in mammals, plays critical roles in various physiological and pathological events including cancer progression. The formation of N-glycan branches catalyzed by specific N-acetylglucosaminyltransferases [GnT-III, GnT-IVs, GnT-V, GnT-IX (Vb)] and a fucosyltransferase, Fut8, provides functionally diverse N-glycosylated proteins. Aberrations of these branches are often found in cancer cells and are profoundly involved in cancer growth, invasion and metastasis. In this review, we focus on the GlcNAc and fucose branches of N-glycans and describe how their expression is dysregulated in cancer by genetic and nongenetic mechanisms including epigenetics and nucleotide sugar metabolisms. We also survey the roles that these N-glycans play in cancer progression and therapeutics. Finally, we discuss possible applications of our knowledge on basic glycobiology to the development of medicine and biomarkers for cancer therapy.
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Wako, 351-0198, Japan. y.kizuka@riken.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kizuka
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Wako, 351-0198, Japan. dglycotani@riken.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011134:Polysaccharides; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases
keywords: GlcNAc; N-Glycan; cancer; fucose; glycosylation; glycosyltransferase