14-3-3σ downregulation suppresses ICC metastasis via impairing migration, invasion, and anoikis resistance of ICC cells

Cancer Biomark. 2017 Jul 4;19(3):313-325. doi: 10.3233/CBM-160476.

Abstract

Background: 14-3-3σ protein plays an important role in multiple cellular processes. The role of 14-3-3σ in the progression of intrahepatic cholangiocarcinoma (ICC) has not been well understood.

Objective: We performed this research to explore the relationship between 14-3-3σ level and clinical characteristics and prognosis of ICC patients. Besides, we used ICC cell lines HCCC-9810 and RBE to assess the biological function of 14-3-3σ.

Methods: We examined 14-3-3σ expression in 28 ICC tissues and matched paratumor tissues by quantitative real-time PCR and immunohistochemistry. Additionally, ICC tissue array from 100 patients and normal liver tissue array from 24 healthy people were also analyzed by immunohistochemistry. 14-3-3σ was knocked down in ICC cell lines and the functions and mechanisms of 14-3-3σ were assessed.

Results: 14-3-3σ is highly expressed in ICC tissues and high expression of 14-3-3σ correlates poor overall survival in ICC patients. Knocking down of 14-3-3σ in ICC cell lines reduced cells migration, invasion and anoikis resistance. Furthermore, 14-3-3σ-silenced ICC cells showed significantly decreased invasion-related protein MMP2 and MMP9 expression.

Conclusions: Our results demonstrate prognostic value of 14-3-3σ and its role in metastasis, which is associated with ICC cell lines migration, invasion and anoikis resistance.

Keywords: 14-3-3σ intrahepatic cholangiocarcinoma; anoikis resistance; metastasis.

MeSH terms

  • 14-3-3 Proteins / genetics*
  • 14-3-3 Proteins / metabolism
  • Anoikis
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Down-Regulation
  • Exoribonucleases / genetics*
  • Exoribonucleases / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Transfection

Substances

  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • Exoribonucleases
  • SFN protein, human