Elevated Expression of Nuclear Protein Kinase CK2α as a Poor Prognosis Indicator in Lymph Node Cancerous Metastases of Human Thyroid Cancers

  • Guo, Miao (Department of Biochemical and Molecular Biology, Liaoning Medical University) ;
  • Liu, Chao (Department of Biochemical and Molecular Biology, Liaoning Medical University) ;
  • Qi, Feng-Jie (Department of Pathology, First Affiliated Hospital of Liaoning Medical University) ;
  • Zhang, Xiu-Mei (Department of Biochemical and Molecular Biology, Liaoning Medical University) ;
  • Ren, Li-Li (Department of Biochemical and Molecular Biology, Liaoning Medical University) ;
  • Liu, Yi-Meng (Department of Biochemical and Molecular Biology, Liaoning Medical University) ;
  • Meng, Zhi-Chao (Department of Biochemical and Molecular Biology, Liaoning Medical University) ;
  • Zhu, Zhi-Tu (Department of Oncology, First Affiliated Hospital of Liaoning Medical University) ;
  • Xiao, Jian-Ying (Department of Biochemical and Molecular Biology, Liaoning Medical University)
  • Published : 2014.09.15


Aim: To investigate the expression of protein kinase $CK2{\alpha}$ ($CK2{\alpha}$) in human thyroid disease and its relationship with thyroid cancer metastasis. Materials and Methods: Using immunohistochemistry we measured the expression of $CK2{\alpha}$ in 76 benign and malignant human thyroid cancer tissues, including 10 pairs of papillary carcinoma tissues with or without lymph node cancerous metastasis and similarly 10 pairs of lymph nodes. Results: The expression of $CK2{\alpha}$ was found to be higher in thyroid carcinoma cases (papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma) than in ones such as chronic lymphocytic thyroiditis, nodular goiter and adenoma. These findings were also confirmed by RT-PCR and Western blotting. More strikingly, elevated expression of $CK2{\alpha}$ in thyroid papillary carcinoma tissues was not only significantly associated with lymph node cancerous metastasis and clinical stage of thyroid cancers; but also correlated with epithelial-mesenchymal transition (EMT) and high tenascin C (TNC) expression. In addition, EMT and high TNC expression in thyroid carcinoma tissues was significantly associated with lymph node cancerous metastasis. Conclusions: Elevated expression of nuclear $CK2{\alpha}$ is a poor prognosis indicator in lymph node cancerous metastasis of human thyroid cancers.


Supported by : Technology Department of Liaoning Province of China


  1. Acloque H, Adams MS, ONE MORE, et al (2009). Epithelialmesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest, 119, 1438-49.
  2. Ahmad KA, Wang G, ONE MORE, et al (2008). Protein kinase CK2--a key suppressor of apoptosis. Adv Enzyme Regul, 48, 179-87.
  3. Asa SL, Bedard YC, (2000). Fine-needle aspiration cytology and histopathology. InClark OH, Noguchi S (eds.). Thyroid cancer. Diagnosis and treatment. St. Louis, MO: Quality Medical Publishing, Inc, 2000, 39 - 104.
  4. Atula T, Hedstrom J, Finne P, et al (2003). Tenascin-C expression and its prognostic significance in oral and pharyngeal squamous cell carcinoma. Anticancer Res, 23, 3051-6.
  5. Boerner SL, Asa SL, Biopsy interpretation of the thyroid. Philadelphia, PA: Lippincott Williams & Wilkins. 2009.
  6. Brahma B1, Yulian ED, Ramli M, et al (2013). Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma. Asian Pac J Cancer Prev, 14, 31-7
  7. Buchou T, Vernet M, Blond O, et al (2003). Disruption of the regulatory beta subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality. Mol Cell Biol, 23, 908-15.
  8. Dominguez I, Sonenshein GE, Seldin DC (2009). Protein kinase CK2 in health and disease: CK2 and its role in Wnt and NFkappaB signaling: linking development and cancer. Cell Mol Life Sci, 66, 1850-7.
  9. Duncan JS, Litchfield DW (2008). Too much of a good thing: the role of protein kinase CK2 in tumorigenesis and prospects for therapeutic inhibition of CK2. Biochim Biophys Acta, 1784, 33-47.
  10. Faust RA, Gapany M, Tristani P, et al (1996). Elevated protein kinase CK2 activity in chromatin of head and neck tumors: association with malignant transformation. Cancer Lett, 101, 31-5.
  11. Giusiano S, Cochet C, Filhol O, et al (2011). Protein kinase CK2alpha subuit over-expression correlates with metastatic risk in breast carcinomas: quantitative immunohistochemistry in tissue microarrays. Eur J Cancer, 47, 792-801.
  12. Guerra B (2006). Protein kinase CK2 subunits are positive regulators of AKT kinase. Int J Oncol , 28, 685-93.
  13. Guo C, Yu S, Davis AT, Ahmed K (1999). Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells. Cancer Res, 59, 1146-51.
  14. Howlader N (2012). SEER Cancer Statistics Review 1975-2009 (Vintage 2009 Populations).
  15. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  16. Kim JS, Eom JI, et al (2007). Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia. Clin Cancer Res, 13, 1019-28.
  17. Koperek O, Prinz A, et al (2009). Tenascin C in medullary thyroid microcarcinoma and C-cell hyperplasia. Virchows Arch, 455, 43-8.
  18. Landesman-Bollag E, Song DH, et al (2001). Protein kinase CK2: signaling and tumorigenesis in the mammary gland. Mol Cell Biochem, 227, 153-65.
  19. Laramas M, Pasquier D, Filhol O, et al (2007). Nuclear localization of protein kinase CK2 catalytic subunit (CK2alpha) is associated with poor prognostic factors in human prostate cancer. Eur J Cancer, 43, 928-34.
  20. Leins A, Riva P, Lindstedt R, et al (2003). Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Cancer , 98, 2430-9.
  21. Lin KY, Tai C, Hsu JC, et al (2011). Overexpression of nuclear protein kinase CK2 alpha catalytic subunit (CK2alpha) as a poor prognosticator in human colorectal cancer. PLoS One, 6, 17193.
  22. Litchfield DW (2003). Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J, 369, 1-15.
  23. Lyons AJ, Jones J (2007). Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg, 36, 671-9.
  24. Mackie EJ, Chiquet-Ehrismann R, Pearson CA, et al (1987). Tenascin is a stromal marker for epithelial malignancy in the mammary gland. Proc Natl Acad Sci USA, 84, 4621-5.
  25. Midwood KS, Hussenet T, Langlois B, Orend G. (2011). Advances in tenascin-C biology. Cell Mol Life Sci, 68, 3175-99.
  26. Oskarsson T, Acharyya S, Zhang XH, et al (2011). Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med, 17, 867-874.
  27. O-charoenrat P, Rusch V, Talbot SG, et al (2004). Casein kinase II alpha subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lung. Clin Cancer Res, 10, 5792-5803.
  28. Ranjbari N, Almasi S, Mohammadi-Asl J, Rahim F (2013). BRAF mutations in Iranian patients with papillary thyroid carcinoma. Asian Pac J Cancer Prev, 14, 2521-3
  29. Seldin DC, Lou DY, et al (2008). Gene targeting of CK2 catalytic subunits. Mol Cell Biochem, 316, 141-7.
  30. Stalter G, Siemer S, Becht E, et al (1994). Asymmetric expression of protein kinase CK2 subunits in human kidney tumors. Biochem Biophys Res Commun, 202, 141-7.
  31. Tseleni-Balafouta S, Gakiopoulou H, Fanourakis G, et al (2006). Tenascin-C protein expression and mRNA splice variants in thyroid carcinoma. Exp Mol Pathol, 80, 177-82.
  32. Xiao J, Liu C, Hou J, et al (2011). Ser149 is another potential PKA phosphorylation target of Cdc25B in G2/M transition of fertilized mouse eggs. J Biol Chem , 286, 10356-66.
  33. Zhang S, Long H, Yang YL, et al (2013). Inhibition of CK2alpha down-regulates Notch1 signalling in lung cancer cells. J Cell Mol Med , 17, 854-62.

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