+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Enzymes for N-Glycan Branching and Their Genetic and Nongenetic Regulation in Cancer

      , *
      cancer, fucose, GlcNAc, N-Glycan, glycosylation, glycosyltransferase

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          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.

          Related collections

          Most cited references140

          • Record: found
          • Abstract: found
          • Article: not found

          Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease.

          O-GlcNAcylation is the addition of β-D-N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. O-linked N-acetylglucosamine (O-GlcNAc) was not discovered until the early 1980s and still remains difficult to detect and quantify. Nonetheless, O-GlcNAc is highly abundant and cycles on proteins with a timescale similar to protein phosphorylation. O-GlcNAc occurs in organisms ranging from some bacteria to protozoans and metazoans, including plants and nematodes up the evolutionary tree to man. O-GlcNAcylation is mostly on nuclear proteins, but it occurs in all intracellular compartments, including mitochondria. Recent glycomic analyses have shown that O-GlcNAcylation has surprisingly extensive cross talk with phosphorylation, where it serves as a nutrient/stress sensor to modulate signaling, transcription, and cytoskeletal functions. Abnormal amounts of O-GlcNAcylation underlie the etiology of insulin resistance and glucose toxicity in diabetes, and this type of modification plays a direct role in neurodegenerative disease. Many oncogenic proteins and tumor suppressor proteins are also regulated by O-GlcNAcylation. Current data justify extensive efforts toward a better understanding of this invisible, yet abundant, modification. As tools for the study of O-GlcNAc become more facile and available, exponential growth in this area of research will eventually take place.
            • Record: found
            • Abstract: found
            • Article: not found

            Molecular signals of epigenetic states.

            Epigenetic signals are responsible for the establishment, maintenance, and reversal of metastable transcriptional states that are fundamental for the cell's ability to "remember" past events, such as changes in the external environment or developmental cues. Complex epigenetic states are orchestrated by several converging and reinforcing signals, including transcription factors, noncoding RNAs, DNA methylation, and histone modifications. Although all of these pathways modulate transcription from chromatin in vivo, the mechanisms by which epigenetic information is transmitted through cell division remain unclear. Because epigenetic states are metastable and change in response to the appropriate signals, a deeper understanding of their molecular framework will allow us to tackle the dysregulation of epigenetics in disease.
              • Record: found
              • Abstract: found
              • Article: not found

              Metabolism, cell surface organization, and disease.

              Genetic information flows from DNA to macromolecular structures-the dominant force in the molecular organization of life. However, recent work suggests that metabolite availability to the hexosamine and Golgi N-glycosylation pathways exerts control over the assembly of macromolecular complexes on the cell surface and, in this capacity, acts upstream of signaling and gene expression. The structure and number of N-glycans per protein molecule cooperate to regulate lectin binding and thereby the distribution of glycoproteins at the cell surface. Congenital disorders of glycosylation provide insight as extreme hypomorphisms, whereas milder deficiencies may encompass many common chronic conditions, including autoimmunity, metabolic syndrome, and aging. Copyright 2009 Elsevier Inc. All rights reserved.

                Author and article information

                Role: Academic Editor
                28 April 2016
                June 2016
                : 6
                : 2
                : 25
                Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Wako, 351-0198, Japan; y.kizuka@ 123456riken.jp
                Author notes
                [* ]Correspondence: dglycotani@ 123456riken.jp or rvw.tani@ 123456sanken.osaka-u.ac.jp ; Tel.: +81-48-467-9616
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 23 March 2016
                : 21 April 2016

                cancer, fucose, glcnac, n-glycan, glycosylation, glycosyltransferase


                Comment on this article