The role of TAK1 expression in thyroid cancer

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14449-56. eCollection 2015.

Abstract

Objective: To investigate the expression, significance, and role of transforming growth factor β-activated kinase 1 (TAK1) in human thyroid cancer tissue.

Methods: The data of 101 patients with thyroid cancer who underwent surgical treatment at our hospital from June 2001 to March 2010 were collected. All the patients were diagnosed with thyroid cancer by post-operative pathological examination. Immunohistochemistry staining was performed to detect the expression of TAK1 protein in thyroid cancer tissue and the adjacent tissues, and correlation analysis was performed to explore the relationships between TAK1 expression level and clinical and pathological features and the patient's prognosis. In addition, thyroid cancer cells (BCPAP) were cultured in vitro to investigate the role of TAK1 in the proliferation, invasion, and apoptosis of thyroid cancer cells and the possible mechanisms of its action.

Results: The TAK1 expression rate was 78.2% in human thyroid cancer tissue, which was significantly higher than in the adjacent normal tissues (14.9%) (P < 0.05). The TAK1 expression level was unrelated to the patient's age, gender, and histological type (P > 0.05) and was closely related to the clinical stage and lymph node metastasis (P < 0.05). Moreover, the five-year survival rate of patients with TAK1 expression was significantly lower than those without TAK1 expression (P = 0.019). In vitro, 5Z-7-oxozeaenol, a selective TAK1 inhibitor, significantly inhibited the proliferation and invasion and promoted the apoptosis of thyroid cancer cells, possibly due to its inhibition of the activation of the nuclear factor-κB (NF-κB) signaling pathway.

Conclusion: TAK1 may be an important factor involved in the pathogenesis of thyroid cancer, and targeted down-regulation of TAK1 may improve the prognosis of patients with thyroid cancer.

Keywords: TAK1; Thyroid cancer; apoptosis; invasion; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • China
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • MAP Kinase Kinase Kinases / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction
  • Thyroid Neoplasms / enzymology*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7