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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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Correlation of 14-3-3σ expression with HSF-1 and HSP70 in HCC tumors. (A) Representative expression of HSF-1 and HSP70 in primary HCC tumors as well as negative control was examined by immunohistochemical analysis. Original magnification, ×200. (B) 14-3-3σ significantly correlates with HSF-1 and HSP70 expression in primary HCC tumors as analyzed by the Chi-square test.
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Figure 3: Correlation of 14-3-3σ expression with HSF-1 and HSP70 in HCC tumors. (A) Representative expression of HSF-1 and HSP70 in primary HCC tumors as well as negative control was examined by immunohistochemical analysis. Original magnification, ×200. (B) 14-3-3σ significantly correlates with HSF-1 and HSP70 expression in primary HCC tumors as analyzed by the Chi-square test.

Mentions: To further show that 14-3-3σ induces HSF-1α/HSP70 in HCC, we examined and compared the expression of HSF-1α/HSP70 with 14-3-3σ by immunohistochemical staining in clinical HCC specimens. Both HSF-1α and HSP70 expression were correlatively increased in HCC tumors (Figure 3A). The expression of HSF-1α and HSP70 stained positively in 93 of 109 (85.3%) and 66 of 109 (60.6%) of primary HCC tumors, respectively. Furthermore, expression of 14-3-3σ positive tumors was significantly correlated with HSF-1α (P < 0.001) and HSP70 (P = 0.032) (Figure 3B). We next analyzed the correlation of HSP70 expression with clinicopathological characteristics and found that positive HSP70 expression was significantly associated with micro-vascular thrombi (P = 0.019) and alpha–fetoprotein levels (P = 0.009) (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)

Correlation of 14-3-3σ expression with HSF-1 and HSP70 in HCC tumors. (A) Representative expression of HSF-1 and HSP70 in primary HCC tumors as well as negative control was examined by immunohistochemical analysis. Original magnification, ×200. (B) 14-3-3σ significantly correlates with HSF-1 and HSP70 expression in primary HCC tumors as analyzed by the Chi-square test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Correlation of 14-3-3σ expression with HSF-1 and HSP70 in HCC tumors. (A) Representative expression of HSF-1 and HSP70 in primary HCC tumors as well as negative control was examined by immunohistochemical analysis. Original magnification, ×200. (B) 14-3-3σ significantly correlates with HSF-1 and HSP70 expression in primary HCC tumors as analyzed by the Chi-square test.
Mentions: To further show that 14-3-3σ induces HSF-1α/HSP70 in HCC, we examined and compared the expression of HSF-1α/HSP70 with 14-3-3σ by immunohistochemical staining in clinical HCC specimens. Both HSF-1α and HSP70 expression were correlatively increased in HCC tumors (Figure 3A). The expression of HSF-1α and HSP70 stained positively in 93 of 109 (85.3%) and 66 of 109 (60.6%) of primary HCC tumors, respectively. Furthermore, expression of 14-3-3σ positive tumors was significantly correlated with HSF-1α (P < 0.001) and HSP70 (P = 0.032) (Figure 3B). We next analyzed the correlation of HSP70 expression with clinicopathological characteristics and found that positive HSP70 expression was significantly associated with micro-vascular thrombi (P = 0.019) and alpha–fetoprotein levels (P = 0.009) (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