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Article

O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy

  • Authors:
    • Yu Cheng
    • Honglun Li
    • Jianlin Li
    • Jisheng Li
    • Yan Gao
    • Baodong Liu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, P.R. China, Department of Radiology, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, P.R. China, Department of Radiology, Penglai Hospital of Traditional Chinese Medicine, Penglai, Shandong 265600, P.R. China, Department of Dermatology, Yankuang Group General Hospital, Zoucheng, Shandong 273500, P.R. China, Department of Ultrasound, Yankuang Group General Hospital, Zoucheng, Shandong 273500, P.R. China
  • Pages: 572-578
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    Published online on: May 30, 2016
       https://doi.org/10.3892/ol.2016.4647
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Abstract

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), a dynamic post-translational modification of nuclear and cytoplasmic proteins, may have a critical role in the regulation of biological cell processes and human cancer. O‑GlcNAcylation is dynamically regulated by O‑GlcNAc transferase (OGT) and O‑GlcNAc hydrolase (OGA). Accumulating evidence suggests that O‑GlcNAcylation is involved in a variety of types of human cancer. However, the exact role of O‑GlcNAcylation in tumor pathogenesis or progression remains to be established. Computed tomography scans of patients with anaplastic thyroid carcinoma (ATC) reveal a rapid growth rate and invasion. The present study demonstrated that O‑GlcNAcylation accelerates the progression of ATC. The global O‑GlcNAc level of intracellular proteins was increased by overexpression of OGT or downregulation of OGA activity with the specific inhibitor Thiamet‑G. By contrast, the global O‑GlcNAc level was decreased by silencing of OGT. MTT assay indicated that O‑GlcNAcylation significantly promotes cell proliferation. Furthermore, O‑GlcNAcylation enhanced cellular biological functions, such as colony formation ability, migration and invasion, of ATC cells in vitro. The findings of the present study suggest that O‑GlcNAcylation is associated with malignant properties of thyroid cancer, and may be a potential target for the diagnosis and treatment of thyroid cancer.
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1 

Zachara NE, O'Donnell N, Cheung WD, Mercer JJ, Marth JD and Hart GW: Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress. A survival response of mammalian cells. J Biol Chem. 279:30133–30142. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Hart GW, Housley MP and Slawson C: Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature. 446:1017–1022. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Wells L, Vosseller K and Hart GW: Glycosylation of nucleocytoplasmic proteins: Signal transduction and O-GlcNAc. Science. 291:2376–2378. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Hanover JA: Glycan-dependent signaling: O-linked N-acetylglucosamine. FASEB J. 15:1865–1876. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Dias WB and Hart GW: O-GlcNAc modification in diabetes and Alzheimer's disease. Mol Biosyst. 3:766–772. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Lazarus BD, Love DC and Hanover JA: O-GlcNAc cycling: Implications for neurodegenerative disorders. Int J Biochem Cell Biol. 41:2134–2146. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Hart GW, Slawson C, Ramirez-Correa G and Lagerlof O: Cross talk between O-GlcNAcylation and phosphorylation: Roles in signaling, transcription, and chronic disease. Annu Rev Biochem. 80:825–858. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Yuzwa SA and Vocadlo DJ: O-GlcNAc and neurodegeneration: Biochemical mechanisms and potential roles in Alzheimer's disease and beyond. Chem Soc Rev. 43:6839–6858. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Caldwell SA, Jackson SR, Shahriari KS, Lynch TP, Sethi G, Walker S, Vosseller K and Reginato MJ: Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene. 29:2831–2842. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Gu Y, Mi W, Ge Y, Liu H, Fan Q, Han C, Yang J, Han F, Lu X and Yu W: GlcNAcylation plays an essential role in breast cancer metastasis. Cancer Res. 70:6344–6351. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Mi W, Gu Y, Han C, Liu H, Fan Q, Zhang X, Cong Q and Yu W: O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim Biophys Acta. 1812:514–519. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Zachara NE and Hart GW: Cell signaling, the essential role of O-GlcNAc! Biochim Biophys Acta. 1761:599–617. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Chou TY, Hart GW and Dang CV: C-Myc is glycosylated at threonine 58: A known phosphorylation site and a mutational hot spot in lymphomas. J Biol Chem. 270:18961–18965. 1995. View Article : Google Scholar : PubMed/NCBI

14 

Kamemura K, Hayes BK, Comer FI and Hart GW: Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins. Alternative glycosylation/phosphorylation of THR-58, a known mutational hot spot of c-Myc in lymphomas, is regulated by mitogens. J Biol Chem. 277:19229–19235. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Hu MI, Vassilopoulou-Sellin R, Lustig R and Lamont JP: Thyroid and parathyroid cancers. Pazdur R, Wagman LD, Camphausen KA and Hoskins WJ: Cancer Management: A Multidisciplinary Approach (11th). UMB Medica. (Norwalk, CT). 1–4. 2008.

16 

Krzeslak A, Pomorski L and Lipinska A: Elevation of nucleocytoplasmic beta-N-acetylglucosaminidase (O-GlcNAcase) activity in thyroid cancers. Int J Mol Med. 25:643–648. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Krześlak A, Jóźwiak P and Lipińska A: Down-regulation of β-N-acetyl-D-glucosaminidase increases Akt1 activity in thyroid anaplastic cancer cells. Oncol Rep. 26:743–749. 2011.PubMed/NCBI

18 

Yang WH, Park SY, Nam HW, Kim Do H, Kang JG, Kang ES, Kim YS, Lee HC, Kim KS and Cho JW: NF{kappa}B activation is associated with its O-GlcNAcylation state under hyperglycemic conditions. Proc Natl Acad Sci USA. 105:17345–17350. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Gu Y, Zhang J, Mi W, Yang J, Han F, Lu X and Yu W: Silencing of GM3 synthase suppresses lung metastasis of murine breast cancer cells. Breast Cancer Res. 10:R12008. View Article : Google Scholar : PubMed/NCBI

20 

Yuzwa SA, Shan X, Macauley MS, Clark T, Skorobogatko Y, Vosseller K and Vocadlo DJ: Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat Chem Biol. 8:393–399. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Okochi T, Seike H, Higashino K, Hada T, Watanabe S, Yamamura Y, Ito F, Matsuda M, Osafune M, Kotake T and Sonoda T: Alteration of hexosaminidase isoenzymes in human renal carcinoma. Cancer Res. 39:1829–1834. 1979.PubMed/NCBI

22 

Narita M, Taniguchi N, Makita A, et al: Elevated activity of beta-hexosaminidase and sulfhydryl modification in the B-variant of human lung cancer. Cancer Res. 43:5037–5042. 1983.PubMed/NCBI

23 

Gil-Martin E, Gil-Seijo S, Nieto-Novoa C and Fernández-Briera A: Elevation of acid glycosidase activities in thyroid and gastric tumors. Int J Biochem Cell Biol. 28:651–657. 1996. View Article : Google Scholar : PubMed/NCBI

24 

Gil-Martín E, Rodríguez-Berrocal FJ, de la Páez Cadena M and Fernández-Briera A: N-acetyl-beta-hexosaminidase activity and isoenzymes in human gastric adenocarcinoma. Oncology. 56:142–154. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Luqmani Y, Temmim L, Memon A, Abdulaziz L, Parkar A, Ali M, Baker H, Motawy M and Fayaz S: Measurment of serum N-acetyl beta glucosaminidase activity in patients with breast cancer. Acta Oncol. 38:649–653. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Oktem F, Yazicilar O, Güvenç MG, Toprak M, Uzun H, Aydin S and Uslu E: Urinary N-acetyl-beta-D-glucosaminidase levels in patients with laryngeal squamous cell carcinoma. J Otolaryngol. 36:233–239. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Wielgat P, Walczuk U, Szajda S, Bień M, Zimnoch L, Mariak Z and Zwierz K: Activity of lysosomal exoglycosidases in human gliomas. J Neurooncol. 80:243–249. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Borzym-Kluczyk M, Olszewska E, Radziejewska I, Lewszuk A and Zwierz K: Isoenzymes of N-acetyl-beta-hexosaminidase in human pleomorphic adenoma and healthy salivary glands: A preliminary study. Clin Chem Lab Med. 46:131–136. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Szajda SD, Snarsk J, Jankowska A, Puchalski Z and Zwierz K: Isoenzymes A and B of N-acetyl-beta-D-hexosaminidase in serum and urine of patients with pancreatic cancer. Hepatogastroenterology. 55:695–698. 2008.PubMed/NCBI

30 

Olszewska E, Borzym-Kluczyk M, Rzewnicki I, Rutkowska J, Knas M, Rogowski M, Waniewska E and Wielgosz R: Hexosaminidase as a new potential marker for larynx cancer. Clin Biochem. 42:1187–1189. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Slawson C, Pidala J and Potter R: Increased N-acetyl-beta-glucosaminidase activity in primary breast carcinomas corresponds to a decrease in N-acetylglucosamine containing proteins. Biochim Biophys Acta. 1537:147–157. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Hanover JA, Krause MW and Love DC: The hexosaminidase signaling pathway: O-GlcNAc cycling in feast or famine. Biochim Biophys Acta. 1800:80–95. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Butkinaree C, Park K and Hart GW: O-linked beta-Nacetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. Biochim Biophys Acta. 1800:96–106. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Shafi R, Iyer SP, Ellies LG, O'Donnell N, Marek KW, Chui D, Hart GW and Marth JD: The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. Proc Natl Acad Sci USA. 97:5735–5739. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Dehennaut V, Lefebvre T, Sellier C, Leroy Y, Gross B, Walker S, Cacan R, Michalski JC, Vilain JP and Bodart JF: O-linked N-acetylglucosaminyltransferase inhibition prevents G2/M transition in Xenopus laevis oocytes. J Biol Chem. 282:12527–12536. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Ho SR, Wang K, Whisenhunt TR, Huang P, Zhu X, Kudlow JE and Paterson AJ: O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress. FEBS Lett. 584:49–54. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Sohn KC, Lee KY, Park JE and Do SI: OGT functions as a catalytic chaperone under heat stress response: A unique defense role of OGT in hyperthermia. Biochem Biophys Res Commun. 322:1045–1051. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Gupta GP and Massagué J: Cancer metastasis: Building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cheng Y, Li H, Li J, Li J, Gao Y and Liu B: O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy. Oncol Lett 12: 572-578, 2016.
APA
Cheng, Y., Li, H., Li, J., Li, J., Gao, Y., & Liu, B. (2016). O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy. Oncology Letters, 12, 572-578. https://doi.org/10.3892/ol.2016.4647
MLA
Cheng, Y., Li, H., Li, J., Li, J., Gao, Y., Liu, B."O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy". Oncology Letters 12.1 (2016): 572-578.
Chicago
Cheng, Y., Li, H., Li, J., Li, J., Gao, Y., Liu, B."O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy". Oncology Letters 12, no. 1 (2016): 572-578. https://doi.org/10.3892/ol.2016.4647
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng Y, Li H, Li J, Li J, Gao Y and Liu B: O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy. Oncol Lett 12: 572-578, 2016.
APA
Cheng, Y., Li, H., Li, J., Li, J., Gao, Y., & Liu, B. (2016). O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy. Oncology Letters, 12, 572-578. https://doi.org/10.3892/ol.2016.4647
MLA
Cheng, Y., Li, H., Li, J., Li, J., Gao, Y., Liu, B."O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy". Oncology Letters 12.1 (2016): 572-578.
Chicago
Cheng, Y., Li, H., Li, J., Li, J., Gao, Y., Liu, B."O‑GlcNAcylation enhances anaplastic thyroid carcinoma malignancy". Oncology Letters 12, no. 1 (2016): 572-578. https://doi.org/10.3892/ol.2016.4647
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