14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma.
14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma.
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14-3-3σ 诱导肝细胞癌中热休克蛋白 70 的表达。
DOI：
10.1186/1471-2407-14-425
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发表时间：
2014-06-12
期刊：
影响因子：
3.8
通讯作者：
Liou JY
中科院分区：
文献类型：
--
作者：
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
14-3-3σ涉及促进各种恶性肿瘤的肿瘤发展。然而，14-3-3σ在肝细胞癌（HCC）肿瘤进展和调节中的临床相关性以及通路阐明仍不清楚。我们用免疫组化方法检测了109例肝癌组织中14-3-3σ的表达。通过用cDNA或siRNA转染进行过表达和敲低实验。蛋白质表达和细胞迁移通过Western blot和Boyden小室测定。在这项研究中，我们发现14-3-3σ在HCC肿瘤中大量表达。稳定或短暂过表达14-3-3σ可诱导肝癌细胞中热休克因子1α（HSF-1α）和热休克蛋白70（HSP 70）的表达。此外，14-3-3σ的表达与HCC肿瘤中的HSF-1α/HSP 70显著相关，并且14-3-3σ和HSP 70的过表达与HCC患者中的微血管血栓相关，这表明14-3-3σ/HSP 70的表达可能参与细胞迁移/侵袭。体外迁移测定的结果表明，14-3-3σ促进细胞迁移，并且14-3-3σ诱导的细胞迁移被HSP 70的siRNA敲低损害。14-3-3σ诱导的HSF-1α/HSP 70表达可被β-catenin的敲低或GSK-3β的激活所消除。提示14-3-3σ可能通过β-catenin/HSF-1α/HSP 70通路参与促进肝癌细胞迁移和肿瘤发生。因此，14-3-3σ单独或与HSP 70组合是HCC的潜在预后生物标志物。
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. 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. 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. 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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通讯作者：
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