14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma
Journal
BMC Cancer
Journal Volume
14
Journal Issue
1
Date Issued
2014
Author(s)
Liu C.-C.
Jan Y.-J.
Liang S.-M.
Chen S.-C.
Lee Y.-M.
Liu T.-A.
Chang T.-C.
Wang J.
Shyue S.-K.
Sung L.-Y.
Liou J.-Y.
Abstract
Background: 14-3-3σ is implicated in promoting tumor development of various malignancies. However, the clinical relevance of 14-3-3σ in hepatocellular carcinoma (HCC) tumor progression and modulation and pathway elucidation remain unclear.Methods: We investigated 14-3-3σ expression in 109 HCC tissues by immunohistochemistry. Overexpression and knockdown experiments were performed by transfection with cDNA or siRNA. Protein expression and cell migration were determined by Western blot and Boyden chamber assay.Results: In this study, we found that 14-3-3σ is abundantly expressed in HCC tumors. Stable or transient overexpression of 14-3-3σ induces the expression of heat shock factor-1α (HSF-1α) and heat shock protein 70 (HSP70) in HCC cells. Moreover, expression of 14-3-3σ significantly correlates with HSF-1α/HSP70 in HCC tumors and both 14-3-3σ and HSP70 overexpression are associated with micro-vascular thrombi in HCC patients, suggesting that 14-3-3σ/HSP70 expression is potentially involved in cell migration/invasion. Results of an in vitro migration assay indicate that 14-3-3σ promotes cell migration and that 14-3-3σ-induced cell migration is impaired by siRNA knockdown of HSP70. Finally, 14-3-3σ-induced HSF-1α/HSP70 expression is abolished by the knockdown of β-catenin or activation of GSK-3β.Conclusions: Our findings indicate that 14-3-3σ participates in promoting HCC cell migration and tumor development via β-catenin/HSF-1α/HSP70 pathway regulation. Thus, 14-3-3σ alone or combined with HSP70 are potential prognostic biomarkers for HCC. ? 2014 Liu et al.; licensee BioMed Central Ltd.
SDGs
Other Subjects
beta catenin; biological marker; complementary DNA; glycogen synthase kinase 3; heat shock protein 70; heat shock transcription factor 1; heat shock transcription factor 1alpha; small interfering RNA; stratifin; unclassified drug; beta catenin; DNA binding protein; exoribonuclease; heat shock protein 70; heat shock transcription factor; protein 14 3 3; SFN protein, human; transcription factor; tumor marker; adult; article; cancer growth; cancer staging; cancer surgery; carcinogenesis; cell invasion; cell migration; cell proliferation; controlled study; female; gene overexpression; gene silencing; genetic transfection; human; human cell; human tissue; immunohistochemistry; in vitro study; liver cell carcinoma; major clinical study; male; protein expression; protein function; quantitative analysis; real time polymerase chain reaction; tumor volume; upregulation; Western blotting; aged; biosynthesis; cell motion; gene expression regulation; genetics; HepG2 cell line; liver cell carcinoma; liver tumor; metabolism; middle aged; pathology; prognosis; signal transduction; 14-3-3 Proteins; Aged; beta Catenin; Carcinoma, Hepatocellular; Cell Movement; DNA-Binding Proteins; Exoribonucleases; Female; Gene Expression Regulation, Neoplastic; Hep G2 Cells; HSP70 Heat-Shock Proteins; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Signal Transduction; Transcription Factors; Tumor Markers, Biological
Publisher
BioMed Central Ltd.
Type
journal article