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14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma.

Liu CC, Jan YJ, Ko BS, Wu YM, Liang SM, Chen SC, Lee YM, Liu TA, Chang TC, Wang J, Shyue SK, Sung LY, Liou JY - BMC Cancer (2014)

Bottom Line: 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.Finally, 14-3-3σ-induced HSF-1α/HSP70 expression is abolished by the knockdown of β-catenin or activation of GSK-3β.Thus, 14-3-3σ alone or combined with HSP70 are potential prognostic biomarkers for HCC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan. liyingsung@ntu.edu.tw.

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.

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14-3-3σ overexpression induces tumor growth. (A) A represtative expression of 14-3-3σ in a primary HCC tumor and in a negative control examined by immunohistochemical analysis. T: tumor; N: non-cancerous cells. Original magnification: ×200. (B) 14-3-3σ expression levels in HCC cell lines were determined by Western blot analysis. Actin was used as a loading control. (C) The rate of cell proliferation was determined by an MTT assay. Scale bars: mean ± SD.
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Figure 1: 14-3-3σ overexpression induces tumor growth. (A) A represtative expression of 14-3-3σ in a primary HCC tumor and in a negative control examined by immunohistochemical analysis. T: tumor; N: non-cancerous cells. Original magnification: ×200. (B) 14-3-3σ expression levels in HCC cell lines were determined by Western blot analysis. Actin was used as a loading control. (C) The rate of cell proliferation was determined by an MTT assay. Scale bars: mean ± SD.

Mentions: To determine the expression of 14-3-3σ in HCC, paraffin-embedded primary HCC tumors with surrounding non-cancerous tissues of 109 patients were examined by immunohistochemical staining. 14-3-3σ was undetected or was stained with the background in non-cancerous cells but had significantly increased expression in 84 of 109 (77.1%) primary HCC tumors (Figure 1A, right panel and Table 1). We next compared 14-3-3σ expression with the clinicopathological characteristics and found that increased 14-3-3σ expression was significantly associated with surgical margin (P = 0.008), capsular formation (P = 0.028) and micro-vascular thrombi (P = 0.001). These results indicate that expression of 14-3-3σ is associated with a more aggressive tumor behavior and a poor prognosis (Table 1).


14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma.

Liu CC, Jan YJ, Ko BS, Wu YM, Liang SM, Chen SC, Lee YM, Liu TA, Chang TC, Wang J, Shyue SK, Sung LY, Liou JY - BMC Cancer (2014)

14-3-3σ overexpression induces tumor growth. (A) A represtative expression of 14-3-3σ in a primary HCC tumor and in a negative control examined by immunohistochemical analysis. T: tumor; N: non-cancerous cells. Original magnification: ×200. (B) 14-3-3σ expression levels in HCC cell lines were determined by Western blot analysis. Actin was used as a loading control. (C) The rate of cell proliferation was determined by an MTT assay. Scale bars: mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061114&req=5

Figure 1: 14-3-3σ overexpression induces tumor growth. (A) A represtative expression of 14-3-3σ in a primary HCC tumor and in a negative control examined by immunohistochemical analysis. T: tumor; N: non-cancerous cells. Original magnification: ×200. (B) 14-3-3σ expression levels in HCC cell lines were determined by Western blot analysis. Actin was used as a loading control. (C) The rate of cell proliferation was determined by an MTT assay. Scale bars: mean ± SD.
Mentions: To determine the expression of 14-3-3σ in HCC, paraffin-embedded primary HCC tumors with surrounding non-cancerous tissues of 109 patients were examined by immunohistochemical staining. 14-3-3σ was undetected or was stained with the background in non-cancerous cells but had significantly increased expression in 84 of 109 (77.1%) primary HCC tumors (Figure 1A, right panel and Table 1). We next compared 14-3-3σ expression with the clinicopathological characteristics and found that increased 14-3-3σ expression was significantly associated with surgical margin (P = 0.008), capsular formation (P = 0.028) and micro-vascular thrombi (P = 0.001). These results indicate that expression of 14-3-3σ is associated with a more aggressive tumor behavior and a poor prognosis (Table 1).

Bottom Line: 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.Finally, 14-3-3σ-induced HSF-1α/HSP70 expression is abolished by the knockdown of β-catenin or activation of GSK-3β.Thus, 14-3-3σ alone or combined with HSP70 are potential prognostic biomarkers for HCC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan. liyingsung@ntu.edu.tw.

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.

Show MeSH
Related in: MedlinePlus