Sialylation is involved in cell fate decision during development, reprogramming and cancer progression

Abstract

Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progression. Sialylation is essential for early embryonic development and the deletion of UDP-GlcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.

Key words： sialylation; cell fate; development; reprogramming; cancer

References

1 Abeln M, Borst KM, Cajic S, Thiesler H, Kats E, Albers I, Kuhn M, Kaever V, Erdmann RB, Munster-Kuhnel A (2017) Sialylation is dispensable for early murine embryonic development in vitro. ChemBioChem 18(13):1305–1316

2 Angata T, Varki A (2002) Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102(2):439–469

3 Angata T, Kerr SC, Greaves DR, Varki NM, Crocker PR, Varki A (2002) Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia. J Biol Chem 277(27):24466–24474

4 Badr HA, Alsadek DM, Darwish AA, Elsayed AI, Bekmanov BO, Khussainova EM, Zhang X, Cho WC, Djansugurova LB, Li CZ (2014) Lectin approaches for glycoproteomics in FDA-approved cancer biomarkers. Expert Rev Proteomics 11(2):227–236

5 Baldus SE, Zirbes TK, Monig SP, Engel S, Monaca E, Rafiqpoor K, Hanisch FG, Hanski C, Thiele J, Pichlmaier H (1998) Histopathological subtypes and prognosis of gastric cancer are correlated with the expression of mucin-associated sialylated antigens: Sialosyl-Lewis(a), Sialosyl-Lewis(x) and sialosyl-Tn. Tumour Biol 19(6):445–453

6 Ballehaninna UK, Chamberlain RS (2012) The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 3(2):105–119

7 Bhide GP, Colley KJ (2017) Sialylation of N-glycans: mechanism, cellular compartmentalization and function. Histochem Cell Biol 147(2):149–174

8 Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, Vitale L, Pelleri MC, Tassani S, Piva F (2013) An estimation of the number of cells in the human body. Ann Human Biol 40(6):463–471

9 Blix G (1936) Über die Kohlenhydratgruppen des Submaxillarismucins. Hoppe-Seyler's Zeitschrift für physiologische Chemie 240(1–2):43–54

10 Blix FG, Gottschalk A, Klenk E (1957) Proposed nomenclature in the field of neuraminic and sialic acids. Nature 179(4569):1088

11 Bonasio R, Tu S, Reinberg D (2010) Molecular signals of epigenetic states. Science 330(6004):612–616

12 Born GV, Palinski W (1985) Unusually high concentrations of sialic acids on the surface of vascular endothelia. Br J Exp Pathol 66(5):543–549

13 Cazet A, Julien S, Bobowski M, Krzewinski-Recchi MA, Harduin-Lepers A, Groux-Degroote S, Delannoy P (2010) Consequences of the expression of sialylated antigens in breast cancer. Carbohydr Res 345(10):1377–1383

14 Chen X, Varki A (2010) Advances in the biology and chemistry of sialic acids. ACS Chem Biol 5(2):163–176

15 Chu CS, Lo PW, Yeh YH, Hsu PH, Peng SH, Teng YC, Kang ML, Wong CH, Juan LJ (2014) O-GlcNAcylation regulates EZH2 protein stability and function. Proc Natl Acad Sci USA 111 (4):1355–1360

16 Close BE, Colley KJ (1998) In vivo autopolysialylation and localization of the polysialyltransferases PST and STX. J Biol Chem 273(51):34586–34593

17 Coates SW, Gurney T Jr, Sommers LW, Yeh M, Hirschberg CB (1980) Subcellular localization of sugar nucleotide synthetases. J Biol Chem 255(19):9225–9229

18 Comb DG, Roseman S (1958) Enzymic synthesis of N-acetyl-Dmannosamine. Biochim Biophys Acta 29(3):653–654

19 Corfield AP (2015) Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys Acta 1850(1):236–252

20 Corfield AP, Myerscough N, Warren BF, Durdey P, Paraskeva C, Schauer R (1999) Reduction of sialic acid O-acetylation in human colonic mucins in the adenoma-carcinoma sequence. Glycoconj J 16(6):307–317

21 Cui HX, Wang H, Wang Y, Song J, Tian H, Xia C, Shen Y (2016) ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules. Oncol Rep 36(6):3317–3324

22 Dalziel M, Whitehouse C, McFarlane I, Brockhausen I, Gschmeissner S, Schwientek T, Clausen H, Burchell JM, Taylor-Papadimitriou J (2001) The relative activities of the C2GnT1 and ST3Gal-I glycosyltransferases determine O-glycan structure and expression of a tumor-associated epitope on MUC1. J Biol Chem 276(14):11007–11015

23 Dao TL, Ip C, Patel J (1980) Serum sialyltransferase and 5’-nucleotidase as reliable biomarkers in women with breast cancer. J Natl Cancer Inst 65(3):529–534

24 Deng LQ, Chen X, Varki A (2013) Exploration of sialic acid diversity and biology using sialoglycan microarrays. Biopolymers 99 (10):650–665

25 Dickson JJ, Messer M (1978) Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk. Biochem J 170(2):407–413

26 Du J, Meledeo MA, Wang Z, Khanna HS, Paruchuri VD, Yarema KJ (2009) Metabolic glycoengineering: sialic acid and beyond. Glycobiology 19(12):1382–1401

27 Du J, Hong S, Dong L, Cheng B, Lin L, Zhao B, Chen YG, Chen X (2015) Dynamic sialylation in transforming growth factor-beta (TGF-beta)-induced epithelial to mesenchymal transition. J Biol Chem 290(19):12000–12013

28 Duraker N, Hot S, Polat Y, Hobek A, Gencler N, Urhan N (2007) CEA, CA 19-9, and CA 125 in the differential diagnosis of benign and malignant pancreatic diseases with or without jaundice. J Surg Oncol 95(2):142–147

29 Eckhardt M, Gerardy-Schahn R (1998) Genomic organization of the murine polysialyltransferase gene ST8SiaIV (PST-1). Glycobiology 8(12):1165–1172

30 Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156

31 Eylar EH, Madoff MA, Brody OV, Oncley JL (1962) The contribution of sialic acid to the surface charge of the erythrocyte. J Biol Chem 237:1992–2000

32 Fleming SC, Smith S, Knowles D, Skillen A, Self CH (1998) Increased sialylation of oligosaccharides on IgG paraproteins–a potential new tumour marker in multiple myeloma. J Clin Pathol 51(11):825–830

33 Fuster MM, Esko JD (2005) The sweet and sour of cancer: Glycans as novel therapeutic targets. Nat Rev Cancer 5(7):526–542

34 Gal B, Ruano MJ, Puente R, Garcia-Pardo LA, Rueda R, Gil A, Hueso P (1997) Developmental changes in UDP-N-acetylglucosamine 2-epimerase activity of rat and guinea-pig liver. Comp Biochem Physiol B: Biochem Mol Biol 118(1):13–15

35 Gerardy-Schahn R, Delannoy P, von Itzstein M (2015) SialoGlyco chemistry and biology II tools and techniques to identify and capture sialoglycans preface. Sialoglyco Chemistry and Biology Ii 367:V–Vii

36 Ghosh S, Roseman S (1961) Enzymatic phosphorylation of N-acetyl-D-mannosamine. Proc Natl Acad Sci USA 47:955–958

37 Hakomori S (1985) Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. Cancer Res 45(6):2405–2414

38 Hamamoto T, Kawasaki M, Kurosawa N, Nakaoka T, Lee YC, Tsuji S (1993) Two step single primer mediated polymerase chain reaction. Application to cloning of putative mouse, beta-galactoside alpha 2,6-sialyltransferase cDNA. Bioorg Med Chem 1(2):141–145

39 Hanover JA (2001) Glycan-dependent signaling: O-linked N-acetylglucosamine. FASEB J 15(11):1865–1876

40 Hasehira K, Tateno H, Onuma Y, Ito Y, Asashima M, Hirabayashi J (2012) Structural and quantitative evidence for dynamic glycome shift on production of induced pluripotent stem cells. Mol Cell Proteomics 11(12):1913–1923

41 Hata K, Tochigi T, Sato I, Kawamura S, Shiozaki K, Wada T, Takahashi K, Moriya S, Yamaguchi K, Hosono M (2015) Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum. Cancer Sci 106(4):383–389

42 Hatano K, Miyamoto Y, Mori M, Nimura K, Nakai Y, Nonomura N, Kaneda Y (2012) Androgen-regulated transcriptional control of sialyltransferases in prostate cancer cells. PLoS ONE 7(2): e31234

43 Henderson M, Kessel D (1977) Alterations in plasma sialyltransferase levels in patients with neoplastic disease. Cancer 39(3):1129–1134

44 Hudak JE, Canham SM, Bertozzi CR (2014) Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nat Chem Biol 10(1):69–75

45 Ikehara Y, Shimizu N, Kono M, Nishihara S, Nakanishi H, Kitamura T, Narimatsu H, Tsuji S, Tatematsu M (1999) A novel glycosyltransferase with a polyglutamine repeat; a new candidate for GD1alpha synthase (ST6GalNAc V)(1). FEBS Lett 463(1–2):92–96

46 James WM, Agnew WS (1987) Multiple oligosaccharide chains in the voltage-sensitive Na channel from electrophorus electricus: evidence for alpha-2,8-linked polysialic acid. Biochem Biophys Res Commun 148(2):817–826

47 Jandus C, Boligan KF, Chijioke O, Liu H, Dahlhaus M, Demoulins T, Schneider C, Wehrli M, Hunger RE, Baerlocher GM (2014) Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Investig 124(4):1810–1820

48 Jiang C, Liu S, He W, Zhang B, Xia L (2017) The prognostic and predictive value of carbohydrate antigen 19-9 in metastatic colorectal cancer patients with first line bevacizumab containing chemotherapy. J Cancer 8(8):1410–1416

49 Jones RB, Dorsett KA, Hjelmeland AB, Bellis SL (2018) The ST6Gal-I sialyltransferase protects tumor cells against hypoxia by enhancing HIF-1α signaling. J Biol Chem 293(15):jbc-RA117

50 Jourdian GW, Swanson AL, Watson D, Roseman S (1964) Isolation of sialic acid 9-phosphatase from human erythrocytes. J Biol Chem 239:PC2714-6

51 Kakugawa Y, Wada T, Yamaguchi K, Yamanami H, Ouchi K, Sato I, Miyagi T (2002) Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression. Proc Natl Acad Sci USA 99(16):10718–10723

52 Kannagi R (2007) Carbohydrate antigen sialyl Lewis a–its pathophysiological significance and induction mechanism in cancer progression. Chang Gung Med J 30(3):189–209

53 Kashef J, Franz CM (2015) Quantitative methods for analyzing cellcell adhesion in development. Dev Biol 401(1):165–174

54 Kiermaier E, Moussion C, Veldkamp CT, Gerardy-Schahn R, de Vries I, Williams LG, Chaffee GR, Phillips AJ, Freiberger F, Imre R (2016) Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science 351(6269):186–190

55 Klenk E (1941) Neuraminsäure, das Spaltprodukt eines neuen Gehirnlipoids. Hoppe-Seyler's Zeitschrift für physiologische Chemie 268(1–2):50–58

56 Kochlamazashvili G, Senkov O, Grebenyuk S, Robinson C, Xiao MF, Stummeyer K, Gerardy-Schahn R, Engel AK, Feig L, Semyanov A (2010) Neural cell adhesion molecule-associated polysialic acid regulates synaptic plasticity and learning by restraining the signaling through GluN2B-containing NMDA receptors. J Neurosci 30(11):4171–4183

57 Kodar K, Stadlmann J, Klaamas K, Sergeyev B, Kurtenkov O (2012) Immunoglobulin G Fc N-glycan profiling in patients with gastric cancer by LC-ESI-MS: relation to tumor progression and survival. Glycoconj J 29(1):57–66

58 Kono M, Takashima S, Liu H, Inoue M, Kojima N, Lee YC, Hamamoto T, Tsuji S (1998) Molecular cloning and functional expression of a fifth-type alpha 2,3-sialyltransferase (mST3Gal V: GM3 synthase). Biochem Biophys Res Commun 253(1):170–175

59 Krzewinski-Recchi MA, Julien S, Juliant S, Teintenier-Lelievre M, Samyn-Petit B, Montiel MD, Mir AM, Cerutti M, Harduin-Lepers A, Delannoy P (2003) Identification and functional expression of a second human beta-galactoside alpha 2,6-sialyltransferase, ST6Gal II. Eur J Biochem 270(5):950–961

60 Kurosawa N, Inoue M, Yoshida Y, Tsuji S (1996) Molecular cloning and genomic analysis of mouse Galbeta 1, 3GalNAc-specific GalNAc alpha2,6-sialyltransferase. J Biol Chem 271(25):15109–15116

61 Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, Demetriou M, Dennis JW (2007) Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129(1):123–134

62 Le Marer N, Laudet V, Svensson EC, Cazlaris H, Van Hille B, Lagrou C, Stehelin D, Montreuil J, Verbert A, Delannoy P (1992) The c-Ha-ras oncogene induces increased expression of beta-galactoside alpha-2, 6-sialyltransferase in rat fibroblast (FR3T3) cells. Glycobiology 2(1):49–56

63 Lee YC, Kojima N, Wada E, Kurosawa N, Nakaoka T, Hamamoto T, Tsuji S (1994) Cloning and expression of cDNA for a new type of Gal beta 1,3GalNAc alpha 2,3-sialyltransferase. J Biol Chem 269 (13):10028–10033

64 Li RH, Liang JL, Ni S, Zhou T, Qing XB, Li HP, He WZ, Chen JK, Li F, Zhuang QA (2010) A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7(1):51–63

65 Liang Y, Xu P, Zou Q, Luo H, Yu W (2018) An epigenetic perspective on tumorigenesis: loss of cell identity, enhancer switching, and NamiRNA network. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2018.09.004

66 Liu XP, Sun H, Qi J, Wang LL, He SW, Liu J, Feng CQ, Chen CL, Li W, Guo YQ (2013) Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming. Nat Cell Biol 15(7):829-+

67 Lowe JB (2 003) Glycan-dependent leukocyte adhesion and recruitment in inflammation. Curr Opin Cell Biol 15(5):531–538

68 Ludwig JA, Weinstein JN (2005) Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 5(11):845–856

69 Macauley MS, Crocker PR, Paulson JC (2014) Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol 14(10):653–666

70 Macbeth RALBJG (1962) Plasma glycoproteins in various disease states including carcinoma. Cancer Res 22(10):1170–1176

71 Margolis RK, Margolis RU (1983) Distribution and characteristics of polysialosyl oligosaccharides in nervous tissue glycoproteins. Biochem Biophys Res Commun 116(3):889–894

72 Melo-Braga MN, Schulz M, Liu QY, Swistowski A, Palmisano G, Engholm-Keller K, Jakobsen L, Zeng XM, Larsen MR (2014)Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells. Mol Cell Proteomics 13(1):311–328

73 Mincarelli L, Lister A, Lipscombe J, Macaulay IC (2018) Defining cell identity with single-cell omics. Proteomics 18(18):e1700312

74 Miyagi T, Takahashi K, Hata K, Shiozaki K, Yamaguchi K (2012) Sialidase significance for cancer progression. Glycoconj J 29(8–9):567–577

75 Moris N, Pina C, Arias AM (2016) Transition states and cell fate decisions in epigenetic landscapes. Nat Rev Genet 17(11):693–703

76 Moyer VA, Force USPST (2012) Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 157(2):120–134

77 Muhlenhoff M, Rollenhagen M, Werneburg S, Gerardy-Schahn R, Hildebrandt H (2013) Polysialic acid: versatile modification of NCAM, SynCAM 1 and neuropilin-2. Neurochem Res 38(6):1134–1143

78 Nakagoe T, Sawai T, Tsuji T, Jibiki M, Nanashima A, Yamaguchi H, Kurosaki N, Yasutake T, Ayabe H (2001) Circulating sialyl Lewis (x), sialyl Lewis(a), and sialyl Tn antigens in colorectal cancer patients: multivariate analysis of predictive factors for serum antigen levels. J Gastroenterol 36(3):166–172

79 Nicoll G, Avril T, Lock K, Furukawa K, Bovin N, Crocker PR (2003) Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and-independent mechanisms. Eur J Immunol 33(6):1642–1648

80 Nomura H, Tamada Y, Miyagi T, Suzuki A, Taira M, Suzuki N, Susumu N, Irimura T, Aoki D (2006) Expression of NEU3 (plasma membrane-associated sialidase) in clear cell adenocarcinoma of the ovary: its relationship with T factor of pTNM classification. Oncol Res 16(6):289–297

81 O’Reilly MK, Paulson JC (2009) Siglecs as targets for therapy in immune-cell-mediated disease. Trends Pharmacol Sci 30(5):240–248

82 Okajima T, Fukumoto S,Miyazaki H, Ishida H, Kiso M, Furukawa K, Urano T, Furukawa K (1999) Molecular cloning of a novel alpha 2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids. J Biol Chem 274(17):11479–11486

83 Okajima T, Chen HH, Ito H, Kiso M, Tai T, Furukawa K, Urano T, Furukawa K (2000) Molecular cloning and expression of mouse GD1alpha/GT1aalpha/GQ1balpha synthase (ST6GalNAc VI) gene. J Biol Chem 275(10):6717–6723

84 Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Stanworth D, Rademacher TW, Mizuochi T, Taniguchi T, Matsuta K (1985) Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 316(6027):452–457

85 Pihikova D, Kasak P, Kubanikova P, Sokol R, Tkac J (2016) Aberrant sialylation of a prostate-specific antigen: Electrochemical labelfree glycoprofiling in prostate cancer serum samples. Anal Chim Acta 934:72–79

86 Pinho SS, Reis CA (2015) Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 15(9):540–555

87 Pucic M, Knezevic A, Vidic J, Adamczyk B, Novokmet M, Polasek O, Gornik O, Supraha-Goreta S, Wormald MR, Redzic I (2011) High throughput isolation and glycosylation analysis of IgGvariability and heritability of the IgG glycome in three isolated human populations. Mol Cell Proteomics 10(10):M111 010090

88 Raval GN, Patel DD, Parekh LJ, Patel JB, Shah MH, Patel PS (2003) Evaluation of serum sialic acid, sialyltransferase and sialoproteins in oral cavity cancer. Oral Dis 9(3):119–128

89 Roseman S, Jourdian GW, Watson D, Rood R (1961) Enzymatic synthesis of sialic acid 9-phosphates. Proc Natl Acad Sci USA 47:958–961

90 Saito S, Onuma Y, Ito Y, Tateno H, Toyoda M, Hidenori A, Nishino K, Chikazawa E, Fukawatase Y, Miyagawa Y (2011) Possible linkages between the inner and outer cellular states of human induced pluripotent stem cells. BMC Syst Biol 5(Suppl 1):S17

91 Sakuma K, Aoki M, Kannagi R (2012) Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition. Proc Natl Acad Sci USA 109(20):7776–7781

92 Saldova R, Wormald MR, Dwek RA, Rudd PM (2008) Glycosylation changes on serum glycoproteins in ovarian cancer may contribute to disease pathogenesis. Dis Markers 25(4–5):219–232

93 Santos-Silva F, Fonseca A, Caffrey T, Carvalho F, Mesquita P, Reis C, Almeida R, David L, Hollingsworth MA (2005) Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism. Glycobiology 15(5):511–517

94 Sasaki K, Watanabe E, Kawashima K, Sekine S, Dohi T, Oshima M, Hanai N, Nishi T, Hasegawa M (1993) Expression cloning of a novel Gal beta (1-3/1-4) GlcNAc alpha 2,3-sialyltransferase using lectin resistance selection. J Biol Chem 268(30):22782–22787

95 Sato C, Kitajima K (2013) Disialic, oligosialic and polysialic acids: distribution, functions and related disease. J Biochem 154(2):115–136

96 Sawhney H, Kumar CA (2011) Correlation of serum biomarkers (TSA & LSA) and epithelial dysplasia in early diagnosis of oral precancer and oral cancer. Cancer Biomark 10(1):43–49

97 Schroeder FH, Hugosson J, Roobol MJ, Tammela TLJ, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M (2009) Screening and Prostate-Cancer Mortality in a Randomized European Study. N Engl J Med 360(13):1320–1328

98 Schultz MJ, Holdbrooks AT, Chakraborty A, Grizzle WE, Landen CN, Buchsbaum DJ, Conner MG, Arend RC, Yoon KJ, Klug CA (2016) The tumor-associated glycosyltransferase ST6Gal-I regulates stem cell transcription factors and confers a cancer stem cell phenotype. Cancer Res 76(13):3978–3988

99 Schwarzkopf M, Knobeloch KP, Rohde E, Hinderlich S, Wiechens N, Lucka L, Horak I, Reutter W, Horstkorte R (2002) Sialylation is essential for early development in mice. Proc Natl Acad Sci USA 99(8):5267–5270

100 Seales EC, Jurado GA, Singhal A, Bellis SL (2003) Ras oncogene directs expression of a differentially sialylated, functionally altered beta1 integrin. Oncogene 22(46):7137–7145

101 Seales EC, Shaikh FM, Woodard-Grice AV, Aggarwal P, McBrayer AC, Hennessy KM, Bellis SL (2005) A protein kinase C/Ras/ERK signaling pathway activates myeloid fibronectin receptors by altering beta1 integrin sialylation. J Biol Chem 280(45):37610–37615

102 Shah MH, Telang SD, Shah PM, Patel PS (2008) Tissue and serum alpha 2-3- and alpha 2-6-linkage specific sialylation changes in oral carcinogenesis. Glycoconj J 25(3):279–290

103 Stojkovic Lalosevic M, Stankovic S, Stojkovic M, Markovic V, Dimitrijevic I, Lalosevic J, Petrovic J, Brankovic M, Pavlovic Markovic A, Krivokapic Z (2017) Can preoperative CEA and CA19-9 serum concentrations suggest metastatic disease in colorectal cancer patients? Hell J Nucl Med 20(1):41–45

104 Suzuki O, Abe M, Hashimoto Y (2015) Sialylation by betagalactoside alpha-2,6-sialyltransferase and N-glycans regulate cell adhesion and invasion in human anaplastic large cell lymphoma. Int J Oncol 46(3):973–980

105 Svennerholm L, Bostrom K, Fredman P, Mansson JE, Rosengren B, Rynmark BM (1989) Human brain gangliosides: developmental changes from early fetal stage to advanced age. Biochim Biophys Acta 1005(2):109–117

106 Swindall AF, Bellis SL (2011) Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells. J Biol Chem 286(26):22982–22990

107 Tajiri M, Ohyama C, Wada Y (2008) Oligosaccharide profiles of the prostate specific antigen in free and complexed forms from the prostate cancer patient serum and in seminal plasma: a glycopeptide approach. Glycobiology 18(1):2–8

108 Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

109 Takashima S, Tachida Y, Nakagawa T, Hamamoto T, Tsuji S (1999) Quantitative analysis of expression of mouse sialyltransferase genes by competitive PCR. Biochem Biophys Res Commun 260(1):23–27

110 Takashima S, Ishida HK, Inazu T, Ando T, Ishida H, Kiso M, Tsuji S, Tsujimoto M (2002) Molecular cloning and expression of a sixth type of alpha 2,8-sialyltransferase (ST8Sia VI) that sialylates O-glycans. J Biol Chem 277(27):24030–24038

111 Theodoratou E, Thaci K, Agakov F, Timofeeva MN, Stambuk J, Pucic-Bakovic M, Vuckovic F, Orchard P, Agakova A, Din FV (2016) Glycosylation of plasma IgG in colorectal cancer prognosis. Sci Rep 6:28098

112 Uckun FM, Goodman P, Ma H, Dibirdik I, Qazi S (2010) CD22 EXON 12 deletion as a pathogenic mechanism of human B-precursor leukemia. Proc Natl Acad Sci USA 107(39):16852–16857

113 van Karnebeek CDM, Bonafe L, Wen XY, Tarailo-Graovac M, Balzano S, Royer-Bertrand B, Ashikov A, Garavelli L, Mammi I, Turolla L (2017) NANS-mediated synthesis of sialic acid is required for brain and skeletal development (vol 48, pg 777, 2016). Nat Genet 49(6):969

114 Varki A (2008) Sialic acids in human health and disease. Trends Mol Med 14(8):351–360

115 Vuckovic F, Theodoratou E, Thaci K, Timofeeva M, Vojta A, Stambuk J, Pucic-Bakovic M, Rudd PM, Derek L, Servis D (2016) IgG glycome in colorectal cancer. Clin Cancer Res 22(12):3078–3086

116 Wang B (2009) Sialic acid is an essential nutrient for brain development and cognition. Annu Rev Nutr 29:177–222

117 Wang B (2012) Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Advances in Nutrition 3(3):465s–472s

118 Wang B, Brand-Miller J, McVeagh P, Petocz P (2001) Concentration and distribution of sialic acid in human milk and infant formulas. Am J Clin Nutr 74(4):510–515

119 Wang B, McVeagh P, Petocz P, Brand-Miller J (2003) Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants. Am J Clin Nutr 78(5):1024–1029

120 Wang YC, Peterson SE, Loring JF (2014) Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res 24(2):143–160

121 Wang YC, Stein JW, Lynch CL, Tran HT, Lee CY, Coleman R, Hatch A, Antontsev VG, Chy HS, O’Brien CM (2015) Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in human pluripotent stem cells. Sci Rep 5:13317

122 Weber KS, Alon R, Klickstein LB (2004) Sialylation of ICAM-2 on platelets impairs adhesion of leukocytes via LFA-1 and DC-SIGN. Inflammation 28(4):177–188

123 Werneburg S, Buettner FF, Erben L, Mathews M, Neumann H, Muhlenhoff M, Hildebrandt H (2016) Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages. Glia 64(8):1314–1330

124 Yabe U, Sato C, Matsuda T, Kitajima K (2003) Polysialic acid in human milk—CD36 is a new member of mammalian polysialic acid-containing glycoprotein. J Biol Chem 278(16):13875–13880

125 Yang X, Qian K (2017) Protein O-GlcNAcylation: emerging mechanisms and functions. Nat Rev Mol Cell Biol 18(7):452–465

126 Yang PMD, Rutishauser U (1994) Role of charge and hydration in effects of polysialic acid on molecular interactions on and between cell membranes. J Biol Chem 269(37):23039–23044

127 Yoneyama T, Ohyama C, Hatakeyama S, Narita S, Habuchi T, Koie T, Mori K, Hidari KIPJ, Yamaguchi M, Suzuki T (2014) Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer. Biochem Biophys Res Commun 448(4):390–396

128 Yoshida Y, Kojima N, Tsuji S (1995) Molecular cloning and characterization of a third type of N-glycan alpha 2,8-sialyltransferase from mouse lung. J Biochem 118(3):658–664

129 Zhang D, Chen BC, Wang YM, Xia P, He CY, Liu YJ, Zhang RQ, Zhang M, Li ZL (2016) Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases. Sci Rep 6:25957

130 Zhao J, Simeone DM, Heidt D, Anderson MA, Lubman DM (2006) Comparative serum glycoproteomics using lectin selected sialic acid glycoproteins with mass spectrometric analysis: Application to pancreatic cancer serum. J Proteome Res 5(7):1792–1802

131 Zhao ZA, Yu Y, Ma HX, Wang XX, Lu X, Zhai Y, Zhang X, Wang H, Li L (2015) The roles of ERAS during cell lineage specification of mouse early embryonic development. Open Biol 5(8):150092

132 Zhao T, Fu Y, Zhu J, Liu Y, Zhang Q, Yi Z, Chen S, Jiao Z, Xu X, Xu J (2018) Single-cell RNA-Seq reveals dynamic early embryonic-like programs during chemical reprogramming. Cell Stem Cell 23(1):31–45 e7

133 Zhou Q, Melton DA (2008) Extreme makeover: converting one cell into another. Cell Stem Cell 3(4):382–388