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O-GlcNAcylation: A Crucial Regulator in Cancer-Associated Biological Events

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Abstract

O-GlcNAcylation, a recently discovered post-translational modification of proteins, plays a crucial role in regulating protein structure and function, and is closely associated with multiple diseases. Research has shown that O-GlcNAcylation is abnormally upregulated in most cancers, promoting disease progression. To elucidate the roles of O-GlcNAcylation in cancer, this review summarizes various cancer-associated biological events regulated by O-GlcNAcylation and the corresponding signaling pathways. This work may provide insights for future studies on the function or underlying mechanisms of O-GlcNAcylation in cancer.

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References

  1. Xue, J., Zhu, L. P., & Wei, Q. (2013). IgG-Fc N-glycosylation at Asn297 and IgA O-glycosylation in the hinge region in health and disease. Glycoconjugate Journal, 30, 735–745. https://doi.org/10.1007/s10719-013-9481-y.

    Article  CAS  PubMed  Google Scholar 

  2. Thomas, D., Rathinavel, A. K. & Radhakrishnan, P. (2021). Altered glycosylation in cancer: a promising target for biomarkers and therapeutics. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1875, 188464. https://doi.org/10.1016/j.bbcan.2020.188464.

    Article  CAS  PubMed  Google Scholar 

  3. Torres, C. R. & Hart, G. W. (1984). Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. Journal of of Biological Chemistry, 259, 3308–3317.

    Article  CAS  Google Scholar 

  4. Issad, T., Masson, E., & Pagesy, P. (2010). O-GlcNAc modification, insulin signaling and diabetic complications. Diabetes & Metabolism, 36, 423–435. https://doi.org/10.1016/j.diabet.2010.09.001.

    Article  CAS  Google Scholar 

  5. Chatham, J. C., Zhang, J., & Wende, A. R. (2021). Role of O-Linked N-Acetylglucosamine protein modification in cellular (Patho)Physiology. Physiological Reviews, 101, 427–493. https://doi.org/10.1152/physrev.00043.2019.

    Article  CAS  PubMed  Google Scholar 

  6. Chan, J. J., Zhang, B., & Chew, X. H., et al. (2022). Pan-cancer pervasive upregulation of 3’ UTR splicing drives tumourigenesis. Nature Cell Biology, 24, 928–939. https://doi.org/10.1038/s41556-022-00913-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sun, L., Zhang, H., & Gao, P. (2022). Metabolic reprogramming and epigenetic modifications on the path to cancer. Protein & Cell, 13, 877–919. https://doi.org/10.1007/s13238-021-00846-7.

    Article  CAS  Google Scholar 

  8. East, M. P. & Johnson, G. L. (2022). Adaptive chromatin remodeling and transcriptional changes of the functional kinome in tumor cells in response to targeted kinase inhibition. Journal of Biological Chemistry, 298, 101525. https://doi.org/10.1016/j.jbc.2021.101525.

    Article  CAS  PubMed  Google Scholar 

  9. Lee, J. B., Pyo, K. H. & Kim, H. R. (2021). Role and function of O-GlcNAcylation in cancer. Cancers, 13. https://doi.org/10.3390/cancers13215365.

  10. Hart, G. W., Slawson, C., & Ramirez-Correa, G., et al. (2011). Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Annual Review of Biochemistry, 80, 825–858. https://doi.org/10.1146/annurev-biochem-060608-102511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen, L., Zhou, Q., & Zhang, P., et al. (2023). Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation. Nature Chemical Biology. https://doi.org/10.1038/s41589-023-01354-x.

  12. Shafi, R., Iyer, S. P., & Ellies, L. G., et al. (2000). The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. Proceedings of the National Academy of Sciences of USA, 97, 5735–5739. https://doi.org/10.1073/pnas.100471497.

    Article  CAS  Google Scholar 

  13. Iyer, S. P., & Hart, G. W. (2003). Roles of the tetratricopeptide repeat domain in O-GlcNAc transferase targeting and protein substrate specificity. Journal of Biological Chemistry, 278, 24608–24616. https://doi.org/10.1074/jbc.M300036200.

    Article  CAS  PubMed  Google Scholar 

  14. Blatch, G. L., & Lassle, M. (1999). The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays, 21, 932–939. 10.1002/(SICI)1521-1878(199911)21:11<932::AID-BIES5>3.0.CO;2-N.

    Article  CAS  PubMed  Google Scholar 

  15. Wrabl, J. O., & Grishin, N. V. (2001). Homology between O-linked GlcNAc transferases and proteins of the glycogen phosphorylase superfamily. Journal Molecular Biology, 314, 365–374. https://doi.org/10.1006/jmbi.2001.5151.

    Article  CAS  Google Scholar 

  16. Roos, M. D., & Hanover, J. A. (2000). Structure of O-linked GlcNAc transferase: mediator of glycan-dependent signaling. Biochemical and Biophysical Research Communications, 271, 275–280. https://doi.org/10.1006/bbrc.2000.2600.

    Article  CAS  PubMed  Google Scholar 

  17. Levine, Z. G., & Walker, S. (2016). The biochemistry of O-GlcNAc transferase: which functions make it essential in mammalian cells? Annual Review of Biochemistry, 85, 631–657. https://doi.org/10.1146/annurev-biochem-060713-035344.

    Article  CAS  PubMed  Google Scholar 

  18. Trapannone, R., Mariappa, D., & Ferenbach, A. T., et al. (2016). Nucleocytoplasmic human O-GlcNAc transferase is sufficient for O-GlcNAcylation of mitochondrial proteins. Biochemical Journal, 473, 1693–1702. https://doi.org/10.1042/BCJ20160092.

    Article  CAS  PubMed  Google Scholar 

  19. Varshney, S., & Stanley, P. (2017). EOGT and O-GlcNAc on secreted and membrane proteins. Biochemical Society Transactions, 45, 401–408. https://doi.org/10.1042/BST20160165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Barua, R., Mizuno, K., & Tashima, Y., et al. (2021). Bioinformatics and functional analyses implicate potential roles for EOGT and L-fringe in pancreatic cancers. Molecules, 26. https://doi.org/10.3390/molecules26040882.

  21. Overdijk, B., Van der Kroef, W. M., & Van Steijn, G. J., et al. (1981). Isolation and further characterization of bovine brain hexosaminidase C. Biochimica et Biophysica Acta, 659, 255–266. https://doi.org/10.1016/0005-2744(81)90052-8.

    Article  CAS  PubMed  Google Scholar 

  22. King, D. T., Males, A., & Davies, G. J., et al. (2019). Molecular mechanisms regulating O-linked N-acetylglucosamine (O-GlcNAc)-processing enzymes. Current Opinion in Chemical Biology, 53, 131–144. https://doi.org/10.1016/j.cbpa.2019.09.001.

    Article  CAS  PubMed  Google Scholar 

  23. Ferron, M., Denis, M., & Persello, A., et al. (2018). Protein O-GlcNAcylation in cardiac pathologies: past, present, future. Frontiers in Endocrinology, 9, 819 https://doi.org/10.3389/fendo.2018.00819.

    Article  PubMed  Google Scholar 

  24. Marshall, S., Bacote, V., & Traxinger, R. R. (1991). Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. Journal of Biological Chemistry, 266, 4706–4712.

  25. Sharma, N. S., Saluja, A. K., & Banerjee, S. (2018). “Nutrient-sensing” and self-renewal: O-GlcNAc in a new role. Journal of Bioenergetics and Biomembrances, 50, 205–211. https://doi.org/10.1007/s10863-017-9735-7.

    Article  CAS  Google Scholar 

  26. Kopanja, D., Chand, V., & O’Brien, E., et al. (2022). Transcriptional repression by FoxM1 suppresses tumor differentiation and promotes metastasis of breast cancer. Cancer Research, 82, 2458–2471. https://doi.org/10.1158/0008-5472.CAN-22-0410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Inoue, Y., Moriwaki, K., & Ueda, Y., et al. (2018). Elevated O-GlcNAcylation stabilizes FOXM1 by its reduced degradation through GSK-3beta inactivation in a human gastric carcinoma cell line, MKN45 cells. Biochemical and Biophysical Research Communications, 495, 1681–1687. https://doi.org/10.1016/j.bbrc.2017.11.179.

    Article  CAS  PubMed  Google Scholar 

  28. Caldwell, S. A., Jackson, S. R., & Shahriari, K. S., et al. (2010). Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene, 29, 2831–2842. https://doi.org/10.1038/onc.2010.41.

    Article  CAS  PubMed  Google Scholar 

  29. Grusche, F. A., Richardson, H. E., & Harvey, K. F. (2010). Upstream regulation of the hippo size control pathway. Current Biology, 20, R574–R582. https://doi.org/10.1016/j.cub.2010.05.023.

    Article  CAS  PubMed  Google Scholar 

  30. Halder, G., & Johnson, R. L. (2011). Hippo signaling: growth control and beyond. Development, 138, 9–22. https://doi.org/10.1242/dev.045500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Moroishi, T., Hayashi, T., & Pan, W. W., et al. (2016). The Hippo pathway kinases LATS1/2 suppress cancer immunity. Cell, 167, 1525–1539. https://doi.org/10.1016/j.cell.2016.11.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pan, D. (2010). The Hippo signaling pathway in development and cancer. Development Cell, 19, 491–505. https://doi.org/10.1016/j.devcel.2010.09.011.

    Article  CAS  Google Scholar 

  33. Misra, J. R., & Irvine, K. D. (2018). The Hippo signaling network and its biological functions. Annual Review of Genetics, 52, 65–87. https://doi.org/10.1146/annurev-genet-120417-031621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hong, A. W., Meng, Z., & Guan, K. L. (2016). The Hippo pathway in intestinal regeneration and disease. Nature Reviews Gastroenterology & Hepatology, 13, 324–337. https://doi.org/10.1038/nrgastro.2016.59.

    Article  CAS  Google Scholar 

  35. Peng, C., Zhu, Y., & Zhang, W., et al. (2017). Regulation of the Hippo-YAP pathway by glucose sensor O-GlcNAcylation. Molecular Cell, 68, 591–604. https://doi.org/10.1016/j.molcel.2017.10.010.

    Article  CAS  PubMed  Google Scholar 

  36. Xu, T. H., Sheng, Z., & Li, Y., et al. (2020). OGT knockdown counteracts high phosphate-induced vascular calcification in chronic kidney disease through autophagy activation by downregulating YAP. Life Science, 261, 118121 https://doi.org/10.1016/j.lfs.2020.118121.

    Article  CAS  Google Scholar 

  37. Guo, H., Zhang, B., & Nairn, A. V., et al. (2017). O-Linked N-Acetylglucosamine (O-GlcNAc) expression levels epigenetically regulate colon cancer tumorigenesis by affecting the cancer stem cell compartment via modulating expression of transcriptional factor MYBL1. Journal of Biological Chemistry, 292, 4123–4137. https://doi.org/10.1074/jbc.M116.763201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lee, Y., & Rio, D. C. (2015). Mechanisms and regulation of alternative pre-mRNA splicing. Annual Review of Biochemistry, 84, 291–323. https://doi.org/10.1146/annurev-biochem-060614-034316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wu, S., & Näär, A. M. (2019). SREBP1-dependent de novo fatty acid synthesis gene expression is elevated in malignant melanoma and represents a cellular survival trait. Scientific Reports Uk, 9, 10369 https://doi.org/10.1038/s41598-019-46594-x.

    Article  CAS  Google Scholar 

  40. Shimano, H., & Sato, R. (2017). SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. Nature Reviews Endocrinology, 13, 710–730. https://doi.org/10.1038/nrendo.2017.91.

    Article  CAS  PubMed  Google Scholar 

  41. Lee, G., Zheng, Y., & Cho, S., et al. (2017). Post-transcriptional regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 signaling. Cell, 171, 1545–1558. https://doi.org/10.1016/j.cell.2017.10.037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang, H. Y., Lin, W., & Dyck, J. A., et al. (1998). SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. Journal of Cell Biology, 140, 737–750. https://doi.org/10.1083/jcb.140.4.737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jang, S. W., Liu, X., & Fu, H., et al. (2009). Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons. Journal of Biological Chemistry, 284, 24512–24525. https://doi.org/10.1074/jbc.M109.026237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tan, W., Jiang, P., & Zhang, W., et al. (2021). Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation. Molecular Cell, 81, 1890–1904. https://doi.org/10.1016/j.molcel.2021.02.009.

    Article  CAS  PubMed  Google Scholar 

  45. Kohtz, J. D., Jamison, S. F., & Will, C. L., et al. (1994). Protein-protein interactions and 5’-splice-site recognition in mammalian mRNA precursors. Nature, 368, 119–124. https://doi.org/10.1038/368119a0.

    Article  CAS  PubMed  Google Scholar 

  46. Ferrer, C. M., Lynch, T. P., & Sodi, V. L., et al. (2014). O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Molecular Cell, 54, 820–831. https://doi.org/10.1016/j.molcel.2014.04.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yi, W., Clark, P. M., & Mason, D. E., et al. (2012). Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science, 337, 975–980. https://doi.org/10.1126/science.1222278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rao, X., Duan, X., & Mao, W., et al. (2015). O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nature Communications, 6, 8468 https://doi.org/10.1038/ncomms9468.

    Article  CAS  PubMed  Google Scholar 

  49. Clark, P. M., Dweck, J. F. & Mason, D. E. et al. (2008). Direct in-gel fluorescence detection and cellular imaging of O-GlcNAc-modified proteins. Journal of the American Chemical Society, 130, 11576–11577. https://doi.org/10.1021/ja8030467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Park, J., Han, D., & Kim, K., et al. (2009). O-GlcNAcylation disrupts glyceraldehyde-3-phosphate dehydrogenase homo-tetramer formation and mediates its nuclear translocation. Biochimica et Biophysica Acta, 1794, 254–262. https://doi.org/10.1016/j.bbapap.2008.10.003.

    Article  CAS  PubMed  Google Scholar 

  51. Sirover, M. A. (2005). New nuclear functions of the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase, in mammalian cells. Journal of Cellular Biochemistry, 95, 45–52. https://doi.org/10.1002/jcb.20399.

    Article  CAS  PubMed  Google Scholar 

  52. Wang, Y., Liu, J., & Jin, X., et al. (2017). O-GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect. Proceedings of the National Academy of Sciences USA, 114, 13732–13737. https://doi.org/10.1073/pnas.1704145115.

    Article  CAS  Google Scholar 

  53. Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011). Otto Warburg’s contributions to current concepts of cancer metabolism. Nature Reviews Cancer, 11, 325–337. https://doi.org/10.1038/nrc3038.

    Article  CAS  PubMed  Google Scholar 

  54. Chen, Y., Bei, J., & Liu, M., et al. (2021). Sublethal heat stress-induced O-GlcNAcylation coordinates the Warburg effect to promote hepatocellular carcinoma recurrence and metastasis after thermal ablation. Cancer Letters, 518, 23–34. https://doi.org/10.1016/j.canlet.2021.06.001.

    Article  CAS  PubMed  Google Scholar 

  55. Song, H., Ma, J., & Bian, Z., et al. (2019). Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma. Signal Transduction and Targeted Therapy, 4, 40 https://doi.org/10.1038/s41392-019-0067-4.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Butkinaree, C., Park, K., & Hart, G. W. (2010). O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. Biochimica et Biophysica Acta, 1800, 96–106. https://doi.org/10.1016/j.bbagen.2009.07.018.

    Article  CAS  PubMed  Google Scholar 

  57. Hart, G. W., Housley, M. P., & Slawson, C. (2007). Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature, 446, 1017–1022. https://doi.org/10.1038/nature05815.

    Article  CAS  PubMed  Google Scholar 

  58. Wang, Z., Gucek, M., & Hart, G. W. (2008). Cross-talk between GlcNAcylation and phosphorylation: site-specific phosphorylation dynamics in response to globally elevated O-GlcNAc. Proceedingss of the National Academy of Sciences USA, 105, 13793–13798. https://doi.org/10.1073/pnas.0806216105.

    Article  Google Scholar 

  59. Huang, H., Wu, Q., & Guo, X., et al. (2021). O-GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity. Journal of Cellular Physiology, 236, 7491–7503. https://doi.org/10.1002/jcp.30385.

    Article  CAS  PubMed  Google Scholar 

  60. Mendonsa, A. M., Na, T. Y., & Gumbiner, B. M. (2018). E-cadherin in contact inhibition and cancer. Oncogene, 37, 4769–4780. https://doi.org/10.1038/s41388-018-0304-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hanover, J. A., Krause, M. W., & Love, D. C. (2012). Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation. Nature Reviews Molecular Cell Biology, 13, 312–321. https://doi.org/10.1038/nrm3334.

    Article  CAS  PubMed  Google Scholar 

  62. Sakabe, K., Wang, Z., & Hart, G. W. (2010). Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proceedings of the National Academy of Sciences USA, 107, 19915–19920. https://doi.org/10.1073/pnas.1009023107.

    Article  Google Scholar 

  63. Fujiki, R., Chikanishi, T., & Hashiba, W., et al. (2009). GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature, 459, 455–459. https://doi.org/10.1038/nature07954.

    Article  CAS  PubMed  Google Scholar 

  64. Xie, X., Wu, Q. & Zhang, K. et al. (2021). O-GlcNAc modification regulates MTA1 transcriptional activity during breast cancer cell genotoxic adaptation. Biochimica et Biophysica Acta (BBA)-General Subjects, 1865, 129930. https://doi.org/10.1016/j.bbagen.2021.129930.

    Article  CAS  PubMed  Google Scholar 

  65. Pitt, J. M., Marabelle, A., & Eggermont, A., et al. (2016). Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Annals of Oncology, 27, 1482–1492. https://doi.org/10.1093/annonc/mdw168.

    Article  CAS  PubMed  Google Scholar 

  66. Burhol, P. G., Waldum, H. L. & Jorde, R. (1981). File and registration systems in a gastroenterological laboratory. Tidsskrift for den Norske Laegeforening: Tidsskrift for Praktisk Medicin, ny Raekke, 101, 1767–1770.

    CAS  PubMed  Google Scholar 

  67. Qiang, A., Slawson, C., & Fields, P. E. (2021). The role of O-GlcNAcylation in immune cell activation. Frontiers in Endocrinology, 12, 596617 https://doi.org/10.3389/fendo.2021.596617.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Shapouri-Moghaddam, A., Mohammadian, S., & Vazini, H., et al. (2018). Macrophage plasticity, polarization, and function in health and disease. Journal of Cellular Physiology, 233, 6425–6440. https://doi.org/10.1002/jcp.26429.

    Article  CAS  PubMed  Google Scholar 

  69. Chang, Y. H., Weng, C. L., & Lin, K. I. (2020). O-GlcNAcylation and its role in the immune system. Journal of Biomedical Science, 27, 57 https://doi.org/10.1186/s12929-020-00648-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rodrigues, M. N., Stanczak, M. A., & Oliveira, I. A., et al. (2020). Hyperglycemia enhances cancer immune evasion by inducing alternative macrophage polarization through increased O-GlcNAcylation. Cancer Immunology Research, 8, 1262–1272. https://doi.org/10.1158/2326-6066.CIR-19-0904.

    Article  Google Scholar 

  71. Ouyang, M., Yu, C., & Deng, X., et al. (2022). O-GlcNAcylation and its role in cancer-associated inflammation. Frontiers in Immunology, 13, 861559 https://doi.org/10.3389/fimmu.2022.861559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Li, X., Zhang, Z., & Li, L., et al. (2017). Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. Journal of Experimental Medicine, 214, 1093–1109. https://doi.org/10.1084/jem.20161105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sung, H., Ferlay, J., & Siegel, R. L., et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca: A Cancer Journal for Clinicians, 71, 209–249. https://doi.org/10.3322/caac.21660.

    Article  PubMed  Google Scholar 

  74. Taparra, K., Wang, H., & Malek, R., et al. (2018). O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis. Journal of Clinical Investigation, 128, 4924–4937. https://doi.org/10.1172/JCI94844.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Tran, P. T., Fan, A. C., & Bendapudi, P. K., et al. (2008). Combined Inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PloS One, 3, e2125 https://doi.org/10.1371/journal.pone.0002125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Podsypanina, K., Politi, K., & Beverly, L. J., et al. (2008). Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proceedings of the National Academy of Sciences USA, 105, 5242–5247. https://doi.org/10.1073/pnas.0801197105.

    Article  Google Scholar 

  77. Chou, T. Y., Hart, G. W., & Dang, C. V. (1995). c-Myc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas. Journal of Biological Chemistry, 270, 18961–18965. https://doi.org/10.1074/jbc.270.32.18961.

    Article  CAS  PubMed  Google Scholar 

  78. Ilkhanizadeh, S., Lau, J., & Huang, M., et al. (2014). Glial progenitors as targets for transformation in glioma. Advances in Cancer Research, 121, 1–65. https://doi.org/10.1016/B978-0-12-800249-0.00001-9.

    Article  CAS  PubMed  Google Scholar 

  79. Buckner, J. C., Brown, P. D., & O’Neill, B. P., et al. (2007). Central nervous system tumors. Mayo Clinic Proceedings, 82, 1271–1286. https://doi.org/10.4065/82.10.1271.

    Article  PubMed  Google Scholar 

  80. Ciraku, L., Bacigalupa, Z. A., & Ju, J., et al. (2022). O-GlcNAc transferase regulates glioblastoma acetate metabolism via regulation of CDK5-dependent ACSS2 phosphorylation. Oncogene, 41, 2122–2136. https://doi.org/10.1038/s41388-022-02237-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Dang, C. V. (2012). Links between metabolism and cancer. Genes & Development, 26, 877–890. https://doi.org/10.1101/gad.189365.112.

    Article  CAS  Google Scholar 

  82. Simic, P., Williams, E. O., & Bell, E. L., et al. (2013). SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis. Cell Reports, 3, 1175–1186. https://doi.org/10.1016/j.celrep.2013.03.019.

    Article  CAS  PubMed  Google Scholar 

  83. Tao, T., He, Z., & Shao, Z., et al. (2016). TAB3 O-GlcNAcylation promotes metastasis of triple negative breast cancer. Oncotarget, 7, 22807–22818. https://doi.org/10.18632/oncotarget.8182.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Jia, C., Li, H., & Fu, D., et al. (2020). GFAT1/HBP/O-GlcNAcylation axis regulates β-catenin activity to promote pancreatic cancer aggressiveness. BioMed Research International, 2020, 1921609 https://doi.org/10.1155/2020/1921609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yang, C., Hu, J. F., & Zhan, Q., et al. (2021). SHCBP1 interacting with EOGT enhances O-GlcNAcylation of NOTCH1 and promotes the development of pancreatic cancer. Genomics, 113, 827–842. https://doi.org/10.1016/j.ygeno.2021.01.010.

    Article  CAS  PubMed  Google Scholar 

  86. Jiang, Y., Liu, Z., & Xu, F., et al. (2018). Aberrant O-glycosylation contributes to tumorigenesis in human colorectal cancer. Journal of Cellular and Molecular Medicine, 22, 4875–4885. https://doi.org/10.1111/jcmm.13752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Orntoft, T. F., Harving, N., & Langkilde, N. C. (1990). O-linked mucin-type glycoproteins in normal and malignant colon mucosa: lack of T-antigen expression and accumulation of Tn and sialosyl-Tn antigens in carcinomas. International Journal of Cancer, 45, 666–672. https://doi.org/10.1002/ijc.2910450416.

    Article  CAS  PubMed  Google Scholar 

  88. Itzkowitz, S. H., Yuan, M., & Montgomery, C. K., et al. (1989). Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Research, 49, 197–204.

  89. Konno, A., Hoshino, Y., & Terashima, S., et al. (2002). Carbohydrate expression profile of colorectal cancer cells is relevant to metastatic pattern and prognosis. Clinical and Experimental Metastasis, 19, 61–70. https://doi.org/10.1023/a:1013879702702.

    Article  CAS  PubMed  Google Scholar 

  90. Schumacher, U., Higgs, D., & Loizidou, M., et al. (1994). Helix pomatia agglutinin binding is a useful prognostic indicator in colorectal carcinoma. Cancer, 74, 3104–3107. 10.1002/1097-0142(19941215)74:12<3104::aid-cncr2820741207>3.0.co;2-0.

    Article  CAS  PubMed  Google Scholar 

  91. Mi, W., Gu, Y., & Han, C., et al. (2011). O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochimica et Biophysica Acta, 1812, 514–519. https://doi.org/10.1016/j.bbadis.2011.01.009.

    Article  CAS  PubMed  Google Scholar 

  92. Liu, Y., & Peng, F. X. (2021). Research progress on O-GlcNAcylation in the occurrence, development, and treatment of colorectal cancer. World Journal Gastrointestinal Surgery, 13, 96–115. https://doi.org/10.4240/wjgs.v13.i2.96.

    Article  Google Scholar 

  93. Castellano, G., Torrisi, E., & Ligresti, G., et al. (2009). The involvement of the transcription factor Yin Yang 1 in cancer development and progression. Cell Cycle, 8, 1367–1372. https://doi.org/10.4161/cc.8.9.8314.

    Article  CAS  PubMed  Google Scholar 

  94. Zhu, G., Qian, M., & Lu, L., et al. (2019) O-GlcNAcylation of YY1 stimulates tumorigenesis in colorectal cancer cells by targeting SLC22A15 and AANAT. Carcinogenesis. https://doi.org/10.1093/carcin/bgz010.

  95. Zhang, X., Ma, L., & Qi, J., et al. (2015). MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy. Molecular and Cellular Biochemistry, 410, 101–110. https://doi.org/10.1007/s11010-015-2542-8.

    Article  CAS  PubMed  Google Scholar 

  96. Nie, H., Ju, H., & Fan, J., et al. (2020). O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth. Nature Communications, 11, 36 https://doi.org/10.1038/s41467-019-13601-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Yu, M., Chu, S., & Fei, B., et al. (2019). O-GlcNAcylation of ITGA5 facilitates the occurrence and development of colorectal cancer. Experimental Cell Research, 382, 111464 https://doi.org/10.1016/j.yexcr.2019.06.009.

    Article  CAS  PubMed  Google Scholar 

  98. Gu, Y., Lu, K., & Yang, G., et al. (2014). Mutation spectrum of six genes in Chinese phenylketonuria patients obtained through next-generation sequencing. Plos One, 9, e94100 https://doi.org/10.1371/journal.pone.0094100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Forshew, T., Murtaza, M., & Parkinson, C., et al. (2012). Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Science Translational Medicine, 4, 136r–168r. https://doi.org/10.1126/scitranslmed.3003726.

    Article  CAS  Google Scholar 

  100. Kim, K. H., & Roberts, C. W. (2016). Targeting EZH2 in cancer. Nature Medicine, 22, 128–134. https://doi.org/10.1038/nm.4036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Zheng, F., Liao, Y. J., & Cai, M. Y., et al. (2015). Systemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets. PloS Genetics, 11, e1004873 https://doi.org/10.1371/journal.pgen.1004873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tiwari, N., Tiwari, V. K., & Waldmeier, L., et al. (2013). Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell, 23, 768–783. https://doi.org/10.1016/j.ccr.2013.04.020.

    Article  CAS  PubMed  Google Scholar 

  103. Tsanou, E., Peschos, D., & Batistatou, A., et al. (2008). The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Research, 28, 3815–3826.

    PubMed  Google Scholar 

  104. Becker, K. F., Rosivatz, E., & Blechschmidt, K., et al. (2007). Analysis of the E-Cadherin repressor snail in primary human cancers. Cells Tissues Organs, 185, 204–212. https://doi.org/10.1159/000101321.

    Article  CAS  PubMed  Google Scholar 

  105. Roy, H. K., Smyrk, T. C., & Koetsier, J., et al. (2005). The transcriptional repressor SNAIL is overexpressed in human colon cancer. Digestive Diseases and Sciences, 50, 42–46. https://doi.org/10.1007/s10620-005-1275-z.

    Article  CAS  PubMed  Google Scholar 

  106. Li, J., Ahmad, M., & Sang, L., et al. (2023). O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. Journal of Biological Chemistry, 104738. https://doi.org/10.1016/j.jbc.2023.104738.

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Funding

This research was supported by National Natural Science Foundation of China (NSFC NO. 82102841 and NSFC NO. 82273094).

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  1. These authors contributed equally: Zhihong Ran, Lei Zhang

Authors and Affiliations

  1. Medical College, Three Gorges University, Yichang, 443000, China

    Zhihong Ran

  2. Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Zhihong Ran, Lulu Chen & Qibin Song

  3. Guangzhou National Laboratory, Guangzhou, 510005, China

    Zhihong Ran, Lei Zhang, Ming Dong & Lulu Chen

  4. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yu Zhang

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Contributions

Z.R. drafted the manuscript. M.D., L.Z., and Y.Z. provided suggestions and revised the manuscript. L.C. and Q.S. conceptualized, wrote, and revised the manuscript. And all authors reviewed and approved the final version of the manuscript.

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Correspondence to Lulu Chen or Qibin Song.

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Ran, Z., Zhang, L., Dong, M. et al. O-GlcNAcylation: A Crucial Regulator in Cancer-Associated Biological Events. Cell Biochem Biophys 81, 383–394 (2023). https://doi.org/10.1007/s12013-023-01146-z

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