Hyperglycemia and aberrant O-GlcNAcylation: contributions to tumor progression

  • Andréia Vasconcelos-dos-Santos
  • Rafaela Muniz de Queiroz
  • Bruno da Costa Rodrigues
  • Adriane R. Todeschini
  • Wagner B. Dias
MINI-REVIEW
  • 109 Downloads

Abstract

A number of cancer types have shown an increased prevalence and a higher mortality rate in patients with hyperglycemic associated pathologies. Although the correlation between diabetes and cancer incidence has been increasingly reported, the underlying molecular mechanisms beyond this association are not yet fully understood. Recent studies have suggested that high glucose levels support tumor progression through multiple mechanisms that are hallmarks of cancer, including cell proliferation, resistance to apoptosis, increased cell migration and invasiveness, epigenetic regulation (hyperglycemic memory), resistance to chemotherapy and altered metabolism. Most of the above occur because hyperglycemia through hexosamine biosynthetic pathway leads to aberrant O-GlcNAcylation of many intracellular proteins that are involved in those mechanisms. Deregulated O-GlcNAcylation is emerging as a general feature of cancer. Despite strong evidence suggesting that aberrant O-GlcNAcylation is or may be involved in the acquisition of all cancer hallmarks, it remains out of the list of the next generation of emerging hallmarks. Here, we discuss some of the current understanding on how hyperglycemia affects cancer cell biology and how aberrant O-GlcNAcylation stands in this context.

Keywords

Hyperglycemia Cancer O-GlcNAcylation Hexosamine biosynthetic pathway 

Notes

Acknowledgements

The authors thank Dr. Frederico Alisson Silva for the critical review of the manuscript. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Fundação do Câncer.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no competing interests.

References

  1. Abdel Rahman AM, Ryczko M, Pawling J, Dennis JW (2013) Probing the hexosamine biosynthetic pathway in human tumor cells by multitargeted tandem mass spectrometry. ACS Chem Biol 8:2053–2062CrossRefGoogle Scholar
  2. Alisson-Silva F, Freire-de-Lima L, Donadio JL, Lucena MC, Penha L, Sa-Diniz JN, Dias WB, Todeschini AR (2013) Increase of O-glycosylated oncofetal fibronectin in high glucose-induced epithelial-mesenchymal transition of cultured human epithelial cells. PLoS One 8:e60471CrossRefGoogle Scholar
  3. Banerjee S, Sangwan V, McGinn O, Chugh R, Dudeja V, Vickers SM, Saluja AK (2013) Triptolide-induced cell death in pancreatic cancer is mediated by O-GlcNAc modification of transcription factor Sp1. J Biol Chem 288:33927–33938CrossRefGoogle Scholar
  4. Bao B, Wang Z, Ali S, Ahmad A, Azmi AS, Sarkar SH, Banerjee S, Kong D, Li Y, Thakur S et al (2012) Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res 5:355–364CrossRefGoogle Scholar
  5. Beckman JA, Creager MA, Libby P (2002) Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA: J Am Med Assoc 287:2570–2581CrossRefGoogle Scholar
  6. Beishline K, Azizkhan-Clifford J (2015) Sp1 and the 'hallmarks of cancer. FEBS J 282:224–258CrossRefGoogle Scholar
  7. Biadgo B, Abebe M (2016) Type 2 diabetes mellitus and its association with the risk of pancreatic carcinogenesis: a review. The Korean J Gastroenterol= Taehan Sohwagi Hakhoe chi 67:168–177CrossRefGoogle Scholar
  8. Biernacka KM, Uzoh CC, Zeng L, Persad RA, Bahl A, Gillatt D, Perks CM, Holly JM (2013) Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2. Endocr Relat Cancer 20:741–751CrossRefGoogle Scholar
  9. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21CrossRefGoogle Scholar
  10. Bond MR, Hanover JA (2013) O-GlcNAc cycling: a link between metabolism and chronic disease. Annu Rev Nutr 33:205–229CrossRefGoogle Scholar
  11. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D et al (2005) Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28:956–962CrossRefGoogle Scholar
  12. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefGoogle Scholar
  13. Brunello A, Kapoor R, Extermann M (2011) Hyperglycemia during chemotherapy for hematologic and solid tumors is correlated with increased toxicity. Am J Clin Oncol 34:292–296CrossRefGoogle Scholar
  14. Caldwell SA, Jackson SR, Shahriari KS, Lynch TP, Sethi G, Walker S, Vosseller K, Reginato MJ (2010) Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 29:2831–2842CrossRefGoogle Scholar
  15. Carvalho-Cruz, P., Alisson-Silva, F., Todeschini, A.R., and Dias, W.B. (2017). Cellular glycosylation senses metabolic changes and modulates cell plasticity during epithelial to mesenchymal transition. Developmental dynamics : an official publication of the American Association of AnatomistsGoogle Scholar
  16. Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L (2004) Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes 53:3226–3232CrossRefGoogle Scholar
  17. Chaiyawat P, Netsirisawan P, Svasti J, Champattanachai V (2014) Aberrant O-GlcNAcylated proteins: new perspectives in breast and colorectal cancer. Front Endocrinol 5:193CrossRefGoogle Scholar
  18. Chatterjee S, Park ES, Soloff MS (2004) Proliferation of DU145 prostate cancer cells is inhibited by suppressing insulin-like growth factor binding protein-2. Int J Urol: Official J Japanese Urol Assoc 11:876–884CrossRefGoogle Scholar
  19. Cheung N, Mitchell P, Wong TY (2010) Diabetic retinopathy. Lancet 376:124–136CrossRefGoogle Scholar
  20. Chocarro-Calvo A, Garcia-Martinez JM, Ardila-Gonzalez S, De la Vieja A, Garcia-Jimenez C (2013) Glucose-induced beta-catenin acetylation enhances Wnt signaling in cancer. Mol Cell 49:474–486CrossRefGoogle Scholar
  21. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159:1160–1167CrossRefGoogle Scholar
  22. Dauphinee SM, Ma M, Too CK (2005) Role of O-linked beta-N-acetylglucosamine modification in the subcellular distribution of alpha4 phosphoprotein and Sp1 in rat lymphoma cells. J Cell Biochem 96:579–588CrossRefGoogle Scholar
  23. Degraff DJ, Aguiar AA, Sikes RA (2009) Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. Am J Transl Res 1:115–130Google Scholar
  24. Del Barco S, Vazquez-Martin A, Cufi S, Oliveras-Ferraros C, Bosch-Barrera J, Joven J, Martin-Castillo B, Menendez JA (2011) Metformin: multi-faceted protection against cancer. Oncotarget 2:896–917CrossRefGoogle Scholar
  25. Dias WB, Hart GW (2007) O-GlcNAc modification in diabetes and Alzheimer's disease. Mol BioSyst 3:766–772CrossRefGoogle Scholar
  26. Dias WB, Cheung WD, Wang Z, Hart GW (2009) Regulation of calcium/calmodulin-dependent kinase IV by O-GlcNAc modification. J Biol Chem 284:21327–21337CrossRefGoogle Scholar
  27. Dias WB, Cheung WD, Hart GW (2012) O-GlcNAcylation of kinases. Biochem Biophys Res Commun 422:224–228CrossRefGoogle Scholar
  28. Dobbs R, Sakurai H, Sasaki H, Faloona G, Valverde I, Baetens D, Orci L, Unger R (1975) Glucagon: role in the hyperglycemia of diabetes mellitus. Science 187:544–547CrossRefGoogle Scholar
  29. Dong C, Yuan T, Wu Y, Wang Y, Fan TW, Miriyala S, Lin Y, Yao J, Shi J, Kang T et al (2013) Loss of FBP1 by snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell 23:316–331CrossRefGoogle Scholar
  30. Dong T, Kang X, Liu Z, Zhao S, Ma W, Xuan Q, Liu H, Wang Z, Zhang Q (2016) Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer. Tumour Biol: J Int Soc OncodevelopBiol Med 37:8159–8168CrossRefGoogle Scholar
  31. Donovan K, Alekseev O, Qi X, Cho W, Azizkhan-Clifford J (2014) O-GlcNAc modification of transcription factor Sp1 mediates hyperglycemia-induced VEGF-A upregulation in retinal cells. Invest Ophthalmol Vis Sci 55:7862–7873CrossRefGoogle Scholar
  32. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A 97:12222–12226CrossRefGoogle Scholar
  33. Duan W, Shen X, Lei J, Xu Q, Yu Y, Li R, Wu E, Ma Q (2014) Hyperglycemia, a neglected factor during cancer progression. Biomed Res Int 2014:461917CrossRefGoogle Scholar
  34. Duan F, Jia D, Zhao J, Wu W, Min L, Song S, Wu H, Wang L, Wang H, Ruan Y et al (2016) Loss of GFAT1 promotes epithelial-to-mesenchymal transition and predicts unfavorable prognosis in gastric cancer. Oncotarget 7:38427–38439CrossRefGoogle Scholar
  35. Etoh T, Kanai Y, Ushijima S, Nakagawa T, Nakanishi Y, Sasako M, Kitano S, Hirohashi S (2004) Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am J Pathol 164:689–699CrossRefGoogle Scholar
  36. Eustice M, Bond MR, Hanover JA (2017) O-GlcNAc cycling and the regulation of nucleocytoplasmic dynamics. Biochem Soc Trans 45:427–436CrossRefGoogle Scholar
  37. Eyers PA, Keeshan K, Kannan N (2017) Tribbles in the 21st century: the evolving roles of tribbles Pseudokinases in biology and disease. Trends Cell Biol 27:284–298CrossRefGoogle Scholar
  38. Ferrer CM, Sodi VL, Reginato MJ (2016) O-GlcNAcylation in cancer biology: linking metabolism and signaling. J Mol Biol 428:3282–3294CrossRefGoogle Scholar
  39. Flores-Lopez LA, Martinez-Hernandez MG, Viedma-Rodriguez R, Diaz-Flores M, Baiza-Gutman LA (2016) High glucose and insulin enhance uPA expression, ROS formation and invasiveness in breast cancer-derived cells. Cell Oncol 39:365–378CrossRefGoogle Scholar
  40. Fogar P, Pasquali C, Basso D, Floreani A, Piva MG, De Paoli M, Melis A, Sperti C, Pedrazzoli S, Plebani M (1998) Transforming growth factor beta, fibrogenesis and hyperglycemia in patients with chronic pancreatitis. J Med 29:277–287Google Scholar
  41. Garcia-Jimenez C, Garcia-Martinez JM, Chocarro-Calvo A, De la Vieja A (2014) A new link between diabetes and cancer: enhanced WNT/beta-catenin signaling by high glucose. J Mol Endocrinol 52:R51–R66CrossRefGoogle Scholar
  42. Garufi A, D'Orazi G (2014) High glucose dephosphorylates serine 46 and inhibits p53 apoptotic activity. J Exp Clin Cancer Res: CR 33:79CrossRefGoogle Scholar
  43. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070CrossRefGoogle Scholar
  44. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D (2010) Diabetes and cancer: a consensus report. Diabetes Care 33:1674–1685CrossRefGoogle Scholar
  45. Guo L, Teng L (2015) YAP/TAZ for cancer therapy: opportunities and challenges (review). Int J Oncol 46:1444–1452CrossRefGoogle Scholar
  46. Gupta C, Kaur J, Tikoo K (2014) Regulation of MDA-MB-231 cell proliferation by GSK-3beta involves epigenetic modifications under high glucose conditions. Exp Cell Res 324:75–83CrossRefGoogle Scholar
  47. Hahn T, Barth S, Hofmann W, Reich O, Lang I, Desoye G (1998) Hyperglycemia regulates the glucose-transport system of clonal choriocarcinoma cells in vitro. A potential molecular mechanism contributing to the adjunct effect of glucose in tumor therapy. Int J Cancer J Int du cancer 78:353–360CrossRefGoogle Scholar
  48. Han I, Kudlow JE (1997) Reduced O glycosylation of Sp1 is associated with increased proteasome susceptibility. Mol Cell Biol 17:2550–2558CrossRefGoogle Scholar
  49. Han L, Ma Q, Li J, Liu H, Li W, Ma G, Xu Q, Zhou S, Wu E (2011) High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. PLoS One 6:e27074CrossRefGoogle Scholar
  50. Han J, Zhang L, Guo H, Wysham WZ, Roque DR, Willson AK, Sheng X, Zhou C, Bae-Jump VL (2015) Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling. Gynecol Oncol 138:668–675CrossRefGoogle Scholar
  51. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRefGoogle Scholar
  52. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  53. Hart GW, Housley MP, Slawson C (2007) Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature 446:1017–1022CrossRefGoogle Scholar
  54. Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O (2011) Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Annu Rev Biochem 80:825–858CrossRefGoogle Scholar
  55. He XY, Yuan YZ (2014) Advances in pancreatic cancer research: moving towards early detection. World J Gastroenterol: WJG 20:11241–11248CrossRefGoogle Scholar
  56. Heilig C, Zaloga C, Lee M, Zhao X, Riser B, Brosius F, Cortes P (1995) Immunogold localization of high-affinity glucose transporter isoforms in normal rat kidney. Lab Invest 73:674–684Google Scholar
  57. Hernandez-Sanchez F, Guzman-Beltran S, Herrera MT, Gonzalez Y, Salgado M, Fabian G, Torres M (2017) High glucose induces O-GlcNAc glycosylation of the vitamin D receptor (VDR) in THP1 cells and in human macrophages derived from monocytes. Cell Biol Int 41:1065–1074CrossRefGoogle Scholar
  58. Hou Y, Zhou M, Xie J, Chao P, Feng Q, Wu J (2017) High glucose levels promote the proliferation of breast cancer cells through GTPases. Breast Cancer (Dove Med Press) 9:429–436Google Scholar
  59. Isoe T, Makino Y, Mizumoto K, Sakagami H, Fujita Y, Honjo J, Takiyama Y, Itoh H, Haneda M (2010) High glucose activates HIF-1-mediated signal transduction in glomerular mesangial cells through a carbohydrate response element binding protein. Kidney Int 78:48–59CrossRefGoogle Scholar
  60. Itkonen HM, Minner S, Guldvik IJ, Sandmann MJ, Tsourlakis MC, Berge V, Svindland A, Schlomm T, Mills IG (2013) O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells. Cancer Res 73:5277–5287CrossRefGoogle Scholar
  61. Iwashita Y, Fukuchi N, Waki M, Hayashi K, Tahira T (2012) Genome-wide repression of NF-kappaB target genes by transcription factor MIBP1 and its modulation by O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase. J Biol Chem 287:9887–9900CrossRefGoogle Scholar
  62. Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, Gans RO, de Vries EG (2010) Metformin: taking away the candy for cancer? Eur J Cancer 46:2369–2380CrossRefGoogle Scholar
  63. James LR, Tang D, Ingram A, Ly H, Thai K, Cai L, Scholey JW (2002) Flux through the hexosamine pathway is a determinant of nuclear factor kappaB- dependent promoter activation. Diabetes 51:1146–1156CrossRefGoogle Scholar
  64. Jeronimo C, Bastian PJ, Bjartell A, Carbone GM, Catto JW, Clark SJ, Henrique R, Nelson WG, Shariat SF (2011) Epigenetics in prostate cancer: biologic and clinical relevance. Eur Urol 60:753–766CrossRefGoogle Scholar
  65. Khan KH, Wong M, Rihawi K, Bodla S, Morganstein D, Banerji U, Molife LR (2016) Hyperglycemia and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitors in phase I trials: incidence, predictive factors, and management. Oncologist 21:855–860CrossRefGoogle Scholar
  66. Kim G, Cao L, Reece EA, Zhao Z (2017) Impact of protein O-GlcNAcylation on neural tube malformation in diabetic embryopathy. Sci Rep 7:11107CrossRefGoogle Scholar
  67. Krechler T, Novotny J, Zeman M, Krska Z, Svestka T, Svab J, Lukas M, Filipova R, Zak A (2004) Pancreatic carcinoma and diabetes mellitus. Cas Lek Cesk 143:97–100Google Scholar
  68. Krzeslak A, Pomorski L, Lipinska A (2011) Expression, localization, and phosphorylation of Akt1 in benign and malignant thyroid lesions. Endocr Pathol 22:206–211CrossRefGoogle Scholar
  69. Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW (2004) Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp Mol Med 36:1–12CrossRefGoogle Scholar
  70. Lee SK, Moon JW, Lee YW, Lee JO, Kim SJ, Kim N, Kim J, Kim HS, Park SH (2015) The effect of high glucose levels on the hypermethylation of protein phosphatase 1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer. J Genet 94:75–85CrossRefGoogle Scholar
  71. Lee C, An D, Park J (2016) Hyperglycemic memory in metabolism and cancer. Horm Mol Biol Clin Invest 26:77–85Google Scholar
  72. Li W, Ma Q, Li J, Guo K, Liu H, Han L, Ma G (2011) Hyperglycemia enhances the invasive and migratory activity of pancreatic cancer cells via hydrogen peroxide. Oncol Rep 25:1279–1287Google Scholar
  73. Li W, Zhang L, Chen X, Jiang Z, Zong L, Ma Q (2016) Hyperglycemia promotes the epithelial-mesenchymal transition of pancreatic cancer via hydrogen peroxide. Oxidative Med Cell Longev 2016:5190314Google Scholar
  74. Li L, Shao M, Peng P, Yang C, Song S, Duan F, Jia D, Zhang M, Zhao J, Zhao R et al (2017) High expression of GFAT1 predicts unfavorable prognosis in patients with hepatocellular carcinoma. Oncotarget 8:19205–19217Google Scholar
  75. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM (2009) New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 32:1620–1625CrossRefGoogle Scholar
  76. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE (2006) Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Res Treat 98:349–356CrossRefGoogle Scholar
  77. Liu B, Wang J, Li M, Yuan Q, Xue M, Xu F, Chen Y (2017) Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury. Oncotarget 8:19413–19426Google Scholar
  78. Lopez R, Arumugam A, Joseph R, Monga K, Boopalan T, Agullo P, Gutierrez C, Nandy S, Subramani R, de la Rosa JM et al (2013) Hyperglycemia enhances the proliferation of non-tumorigenic and malignant mammary epithelial cells through increased leptin/IGF1R signaling and activation of AKT/mTOR. PLoS One 8:e79708CrossRefGoogle Scholar
  79. Lucena MC, Carvalho-Cruz P, Donadio JL, Oliveira IA, de Queiroz RM, Marinho-Carvalho MM, Sola-Penna M, de Paula IF, Gondim KC, McComb ME et al (2016) Epithelial mesenchymal transition induces aberrant glycosylation through Hexosamine biosynthetic pathway activation. J Biol Chem 291:12917–12929CrossRefGoogle Scholar
  80. Luo Z, Zang M, Guo W (2010) AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol 6:457–470CrossRefGoogle Scholar
  81. Luo Y, Ohmori H, Shimomoto T, Fujii K, Sasahira T, Chihara Y, Kuniyasu H (2011) Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon cancer cells. Pathobiol: J Immunopathol, Mol Cell Biol 78:285–290CrossRefGoogle Scholar
  82. Lynch TP, Ferrer CM, Jackson SR, Shahriari KS, Vosseller K, Reginato MJ (2012) Critical role of O-linked beta-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis. J Biol Chem 287:11070–11081CrossRefGoogle Scholar
  83. Ma Z, Vosseller K (2014) Cancer metabolism and elevated O-GlcNAc in oncogenic signaling. J Biol Chem 289:34457–34465CrossRefGoogle Scholar
  84. Ma Z, Vocadlo DJ, Vosseller K (2013) Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-kappaB activity in pancreatic cancer cells. J Biol Chem 288:15121–15130CrossRefGoogle Scholar
  85. Majumdar G, Wright J, Markowitz P, Martinez-Hernandez A, Raghow R, Solomon SS (2004) Insulin stimulates and diabetes inhibits O-linked N-acetylglucosamine transferase and O-glycosylation of Sp1. Diabetes 53:3184–3192CrossRefGoogle Scholar
  86. Martyn JA, Kaneki M, Yasuhara S (2008) Obesity-induced insulin resistance and hyperglycemia: etiologic factors and molecular mechanisms. Anesthesiology 109:137–148CrossRefGoogle Scholar
  87. Masur K, Vetter C, Hinz A, Tomas N, Henrich H, Niggemann B, Zanker KS (2011) Diabetogenic glucose and insulin concentrations modulate transcriptome and protein levels involved in tumour cell migration, adhesion and proliferation. Br J Cancer 104:345–352CrossRefGoogle Scholar
  88. Matsui C, Takatani-Nakase T, Hatano Y, Kawahara S, Nakase I, Takahashi K (2017). Zinc and its transporter ZIP6 are key mediators of breast cancer cell survival under high glucose conditions. FEBS Lett 591:3348–3359Google Scholar
  89. Meagher RB, Mussar KJ (2012) The influence of DNA sequence on epigenome-induced pathologies. Epigenetics Chromatin 5:11CrossRefGoogle Scholar
  90. Mechanick JI (2006) Metabolic mechanisms of stress hyperglycemia. JPEN J Parenter Enteral Nutr 30:157–163CrossRefGoogle Scholar
  91. Meier JJ, Giese A (2015) Diabetes associated with pancreatic diseases. Curr Opin Gastroenterol 31:400–406CrossRefGoogle Scholar
  92. Mi W, Gu Y, Han C, Liu H, Fan Q, Zhang X, Cong Q, Yu W (2011) O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim Biophys Acta 1812:514–519CrossRefGoogle Scholar
  93. Moloughney JG, Kim PK, Vega-Cotto NM, Wu CC, Zhang S, Adlam M, Lynch T, Chou PC, Rabinowitz JD, Werlen G et al (2016) mTORC2 responds to glutamine catabolite levels to modulate the Hexosamine biosynthesis enzyme GFAT1. Mol Cell 63:811–826CrossRefGoogle Scholar
  94. Munkley J, Elliott DJ (2016) Hallmarks of glycosylation in cancer. Oncotarget 7:35478–35489CrossRefGoogle Scholar
  95. Nakajima K, Kitazume S, Angata T, Fujinawa R, Ohtsubo K, Miyoshi E, Taniguchi N (2010) Simultaneous determination of nucleotide sugars with ion-pair reversed-phase HPLC. Glycobiology 20:865–871CrossRefGoogle Scholar
  96. Nathan DM, Bayless M, Cleary P, Genuth S, Gubitosi-Klug R, Lachin JM, Lorenzi G, Zinman B, Group, D.E.R (2013) Diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: advances and contributions. Diabetes 62:3976–3986CrossRefGoogle Scholar
  97. Oki T, Yamazaki K, Kuromitsu J, Okada M, Tanaka I (1999) cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse. Genomics 57:227–234CrossRefGoogle Scholar
  98. Okumura M, Yamamoto M, Sakuma H, Kojima T, Maruyama T, Jamali M, Cooper DR, Yasuda K (2002) Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression. Biochim Biophys Acta 1592:107–116CrossRefGoogle Scholar
  99. Olivier-Van Stichelen S, Guinez C, Mir AM, Perez-Cervera Y, Liu C, Michalski JC, Lefebvre T (2012) The hexosamine biosynthetic pathway and O-GlcNAcylation drive the expression of beta-catenin and cell proliferation. Am J Phys Endocrinol Metab 302:E417–E424CrossRefGoogle Scholar
  100. Olivier-Van Stichelen S, Dehennaut V, Buzy A, Zachayus JL, Guinez C, Mir AM, El Yazidi-Belkoura I, Copin MC, Boureme D, Loyaux D et al (2014) O-GlcNAcylation stabilizes beta-catenin through direct competition with phosphorylation at threonine 41. FASEB J: Official Pub Federation Am Soc Exp Biol 28:3325–3338CrossRefGoogle Scholar
  101. Onodera Y, Nam JM, Bissell MJ (2014) Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. J Clin Invest 124:367–384CrossRefGoogle Scholar
  102. Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19:491–505CrossRefGoogle Scholar
  103. Paneni F, Volpe M, Luscher TF, Cosentino F (2013) SIRT1, p66(Shc), and Set7/9 in vascular hyperglycemic memory: bringing all the strands together. Diabetes 62:1800–1807CrossRefGoogle Scholar
  104. Peng DF, Kanai Y, Sawada M, Ushijima S, Hiraoka N, Kitazawa S, Hirohashi S (2006) DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas. Carcinogenesis 27:1160–1168CrossRefGoogle Scholar
  105. Peng C, Zhu Y, Zhang W, Liao Q, Chen Y, Zhao X, Guo Q, Shen P, Zhen B, Qian X et al (2017) Regulation of the hippo-YAP pathway by glucose sensor O-GlcNAcylation. Mol Cell 68(591–604):e595Google Scholar
  106. Pham LV, Bryant JL, Mendez R, Chen J, Tamayo AT, Xu-Monette ZY, Young KH, Manyam GC, Yang D, Medeiros LJ et al (2016) Targeting the hexosamine biosynthetic pathway and O-linked N-acetylglucosamine cycling for therapeutic and imaging capabilities in diffuse large B-cell lymphoma. Oncotarget 7:80599–80611Google Scholar
  107. Phoomak C, Vaeteewoottacharn K, Silsirivanit A, Saengboonmee C, Seubwai W, Sawanyawisuth K, Wongkham C, Wongkham S (2017) High glucose levels boost the aggressiveness of highly metastatic cholangiocarcinoma cells via O-GlcNAcylation. Sci Rep 7:43842CrossRefGoogle Scholar
  108. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8:915–928CrossRefGoogle Scholar
  109. Qiao Y, Zhang X, Zhang Y, Wang Y, Xu Y, Liu X, Sun F, Wang J (2016) High glucose stimulates tumorigenesis in hepatocellular carcinoma cells through AGER-dependent O-GlcNAcylation of c-Jun. Diabetes 65:619–632CrossRefGoogle Scholar
  110. de Queiroz RM, Carvalho E, Dias WB (2014) O-GlcNAcylation: the sweet side of the cancer. Front Oncol 4:132CrossRefGoogle Scholar
  111. Rajaram S, Baylink DJ, Mohan S (1997) Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 18:801–831Google Scholar
  112. Rajasekar P, O'Neill CL, Eeles L, Stitt AW, Medina RJ (2015) Epigenetic changes in endothelial progenitors as a possible cellular basis for glycemic memory in diabetic vascular complications. J Diabetes Res 2015:436879CrossRefGoogle Scholar
  113. Ramakrishnan P, Clark PM, Mason DE, Peters EC, Hsieh-Wilson LC, Baltimore D (2013) Activation of the transcriptional function of the NF-kappaB protein c-Rel by O-GlcNAc glycosylation. Sci Signal 6:ra75CrossRefGoogle Scholar
  114. Reddy MA, Natarajan R (2011) Epigenetic mechanisms in diabetic vascular complications. Cardiovasc Res 90:421–429CrossRefGoogle Scholar
  115. Saengboonmee C, Seubwai W, Pairojkul C, Wongkham S (2016) High glucose enhances progression of cholangiocarcinoma cells via STAT3 activation. Sci Rep 6:18995CrossRefGoogle Scholar
  116. Safe S, Imanirad P, Sreevalsan S, Nair V, Jutooru I (2014) Transcription factor Sp1, also known as specificity protein 1 as a therapeutic target. Expert Opin Ther Targets 18:759–769CrossRefGoogle Scholar
  117. Shikata K, Ninomiya T, Kiyohara Y (2013) Diabetes mellitus and cancer risk: review of the epidemiological evidence. Cancer Sci 104:9–14CrossRefGoogle Scholar
  118. Slawson C, Copeland RJ, Hart GW (2010) O-GlcNAc signaling: a metabolic link between diabetes and cancer? Trends Biochem Sci 35:547–555CrossRefGoogle Scholar
  119. Sodi VL, Bacigalupa ZA, Ferrer CM, Lee JV, Gocal WA, Mukhopadhyay D, Wellen KE, Ivan M, Reginato MJ (2017). Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. OncogeneGoogle Scholar
  120. Sowers JR, Epstein M, Frohlich ED (2001) Diabetes, hypertension, and cardiovascular disease: an update. Hypertension 37:1053–1059CrossRefGoogle Scholar
  121. Srinivasan V, Sandhya N, Sampathkumar R, Farooq S, Mohan V, Balasubramanyam M (2007) Glutamine fructose-6-phosphate amidotransferase (GFAT) gene expression and activity in patients with type 2 diabetes: inter-relationships with hyperglycaemia and oxidative stress. Clin Biochem 40:952–957CrossRefGoogle Scholar
  122. Staudt LM (2010) Oncogenic activation of NF-kappaB. Cold Spring Harb Perspect Biol 2:a000109CrossRefGoogle Scholar
  123. Thakur R, Mishra DP (2013) Pharmacological modulation of beta-catenin and its applications in cancer therapy. J Cell Mol Med 17:449–456CrossRefGoogle Scholar
  124. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890CrossRefGoogle Scholar
  125. Thomas F, Holly JM, Persad R, Bahl A, Perks CM (2010) Fibronectin confers survival against chemotherapeutic agents but not against radiotherapy in DU145 prostate cancer cells: involvement of the insulin like growth factor-1 receptor. Prostate 70:856–865Google Scholar
  126. Uzoh CC, Perks CM, Bahl A, Holly JM, Sugiono M, Persad RA (2009) PTEN-mediated pathways and their association with treatment-resistant prostate cancer. BJU Int 104:556–561CrossRefGoogle Scholar
  127. Uzoh CC, Holly JM, Biernacka KM, Persad RA, Bahl A, Gillatt D, Perks CM (2011) Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel. Br J Cancer 104:1587–1593CrossRefGoogle Scholar
  128. Vaira S, Friday E, Scott K, Conrad S, Turturro F (2012) Wnt/beta-catenin signaling pathway and thioredoxin-interacting protein (TXNIP) mediate the "glucose sensor" mechanism in metastatic breast cancer-derived cells MDA-MB-231. J Cell Physiol 227:578–586CrossRefGoogle Scholar
  129. Vajaria BN, Patel PS (2017) Glycosylation: a hallmark of cancer? Glycoconj J 34:147–156CrossRefGoogle Scholar
  130. Vasconcelos-Dos-Santos A, Oliveira IA, Lucena MC, Mantuano NR, Whelan SA, Dias WB, Todeschini AR (2015) Biosynthetic machinery involved in aberrant glycosylation: promising targets for developing of drugs against cancer. Front Oncol 5:138CrossRefGoogle Scholar
  131. Vasconcelos-Dos-Santos A, Loponte HF, Mantuano NR, Oliveira IA, de Paula IF, Teixeira LK, de Freitas-Junior JC, Gondim KC, Heise N, Mohana-Borges R et al (2017) Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway. Oncogene 6:e306CrossRefGoogle Scholar
  132. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA (2010) Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 9:3807–3814CrossRefGoogle Scholar
  133. Viedma-Rodriguez R, Martinez-Hernandez MG, Flores-Lopez LA, Baiza-Gutman LA (2017). Epsilon-aminocaproic acid prevents high glucose and insulin induced-invasiveness in MDA-MB-231 breast cancer cells, modulating the plasminogen activator system. Mol Cell Biochem.  https://doi.org/10.1007/s11010-017-3096-8
  134. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R (2009) Diabetes and cancer. Endocr Relat Cancer 16:1103–1123CrossRefGoogle Scholar
  135. Vishvakarma NK, Kumar A, Singh V, Singh SM (2013) Hyperglycemia of tumor microenvironment modulates stage-dependent tumor progression and multidrug resistance: implication of cell survival regulatory molecules and altered glucose transport. Mol Carcinog 52:932–945CrossRefGoogle Scholar
  136. Wahdan-Alaswad R, Fan Z, Edgerton SM, Liu B, Deng XS, Arnadottir SS, Richer JK, Anderson SM, Thor AD (2013) Glucose promotes breast cancer aggression and reduces metformin efficacy. Cell Cycle 12:3759–3769CrossRefGoogle Scholar
  137. Walgren JL, Vincent TS, Schey KL, Buse MG (2003) High glucose and insulin promote O-GlcNAc modification of proteins, including alpha-tubulin. Am J Phys Endocrinol Metab 284:E424–E434CrossRefGoogle Scholar
  138. Warburg O (1956) On the origin of cancer cells. Science 123:309–314Google Scholar
  139. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR, Chandel NS (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A 107:8788–8793CrossRefGoogle Scholar
  140. Wheaton WW, Weinberg SE, Hamanaka RB, Soberanes S, Sullivan LB, Anso E, Glasauer A, Dufour E, Mutlu GM, Budigner GS et al (2014) Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. elife 3:e02242CrossRefGoogle Scholar
  141. WHO (2016) http://www.who.int/diabetes/en/. Accessed 29 Sept 2017
  142. Wright JL, Plymate SR, Porter MP, Gore JL, Lin DW, Hu E, Zeliadt SB (2013) Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer. Prostate Cancer Prostatic Dis 16:204–208Google Scholar
  143. Writing Team for the Diabetes, C., Complications Trial/Epidemiology of Diabetes, I., and Complications Research, G (2003) Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the epidemiology of diabetes interventions and complications (EDIC) study. JAMA: J Am Med Assoc 290:2159–2167CrossRefGoogle Scholar
  144. Xia Y, Shen S, Verma IM (2014) NF-kappaB, an active player in human cancers. Cancer Immunol Res 2:823–830CrossRefGoogle Scholar
  145. Yang X, Qian K (2017) Protein O-GlcNAcylation: emerging mechanisms and functions. Nat Rev Mol Cell Biol 18:452–465CrossRefGoogle Scholar
  146. Yang WH, Park SY, Nam HW, Kim DH, Kang JG, Kang ES, Kim YS, Lee HC, Kim KS, Cho JW (2008) NFkappaB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions. Proc Natl Acad Sci U S A 105:17345–17350CrossRefGoogle Scholar
  147. Yang YR, Kim DH, Seo YK, Park D, Jang HJ, Choi SY, Lee YH, Lee GH, Nakajima K, Taniguchi N et al (2015) Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-kappaB signaling. Oncotarget 6:12529–12542CrossRefGoogle Scholar
  148. Yang C, Peng P, Li L, Shao M, Zhao J, Wang L, Duan F, Song S, Wu H, Zhang J et al (2016a) High expression of GFAT1 predicts poor prognosis in patients with pancreatic cancer. Sci Rep 6:39044CrossRefGoogle Scholar
  149. Yang IP, Tsai HL, Huang CW, Lu CY, Miao ZF, Chang SF, Juo SH, Wang JY (2016b) High blood sugar levels significantly impact the prognosis of colorectal cancer patients through down-regulation of microRNA-16 by targeting Myb and VEGFR2. Oncotarget 7:18837–18850CrossRefGoogle Scholar
  150. Yao B, Xu Y, Wang J, Qiao Y, Zhang Y, Zhang X, Chen Y, Wu Q, Zhao Y, Zhu G et al (2016) Reciprocal regulation between O-GlcNAcylation and tribbles pseudokinase 2 (TRIB2) maintains transformative phenotypes in liver cancer cells. Cell Signal 28:1703–1712CrossRefGoogle Scholar
  151. Yokoyama T, Nakamura T (2011) Tribbles in disease: signaling pathways important for cellular function and neoplastic transformation. Cancer Sci 102:1115–1122CrossRefGoogle Scholar
  152. Zanconato F, Cordenonsi M, Piccolo S (2016) YAP/TAZ at the roots of cancer. Cancer Cell 29:783–803CrossRefGoogle Scholar
  153. Zeng L, Biernacka KM, Holly JM, Jarrett C, Morrison AA, Morgan A, Winters ZE, Foulstone EJ, Shield JP, Perks CM (2010) Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. Endocr Relat Cancer 17:539–551CrossRefGoogle Scholar
  154. Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36:1461–1473CrossRefGoogle Scholar
  155. Zhang W, Liu J, Tian L, Liu Q, Fu Y, Garvey WT (2013) TRIB3 mediates glucose-induced insulin resistance via a mechanism that requires the hexosamine biosynthetic pathway. Diabetes 62:4192–4200CrossRefGoogle Scholar
  156. Zhang JP, Zhang H, Wang HB, Li YX, Liu GH, Xing S, Li MZ, Zeng MS (2014) Down-regulation of Sp1 suppresses cell proliferation, clonogenicity and the expressions of stem cell markers in nasopharyngeal carcinoma. J Transl Med 12:222CrossRefGoogle Scholar
  157. Zhang X, Qiao Y, Wu Q, Chen Y, Zou S, Liu X, Zhu G, Zhao Y, Chen Y, Yu Y et al (2017) The essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis. Nat Commun 8:15280CrossRefGoogle Scholar
  158. Zhao Y, Zhang W, Guo Z, Ma F, Wu Y, Bai Y, Gong W, Chen Y, Cheng T, Zhi F et al (2013) Inhibition of the transcription factor Sp1 suppresses colon cancer stem cell growth and induces apoptosis in vitro and in nude mouse xenografts. Oncol Rep 30:1782–1792CrossRefGoogle Scholar
  159. Zhao W, Chen R, Zhao M, Li L, Fan L, Che XM (2015) High glucose promotes gastric cancer chemoresistance in vivo and in vitro. Mol Med Rep 12:843–850CrossRefGoogle Scholar
  160. Zhou F, Huo J, Liu Y, Liu H, Liu G, Chen Y, Chen B (2016) Elevated glucose levels impair the WNT/beta-catenin pathway via the activation of the hexosamine biosynthesis pathway in endometrial cancer. J Steroid Biochem Mol Biol 159:19–25CrossRefGoogle Scholar
  161. Zhu S, Yao F, Li WH, Wan JN, Zhang YM, Tang Z, Khan S, Wang CH, Sun SR (2013) PKC?-dependent activation of the ubiquitin proteasome system is responsible for high glucose-induced human breast cancer MCF-7 cell proliferation, migration and invasion. Asian Pacific J Cancer Prevention: APJCP 14:5687–5692CrossRefGoogle Scholar
  162. Ziyadeh FN, Sharma K (2003) Overview: combating diabetic nephropathy. J Am Soc Nephrol: JASN 14:1355–1357CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andréia Vasconcelos-dos-Santos
    • 1
  • Rafaela Muniz de Queiroz
    • 1
  • Bruno da Costa Rodrigues
    • 1
  • Adriane R. Todeschini
    • 1
  • Wagner B. Dias
    • 1
  1. 1.Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

Personalised recommendations