A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma.
A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma.
复制标题
靶向分子伴侣 Hsp27 赋予肝细胞癌侵袭性
作者：
Zhang Y;Tao X;Jin G;Jin H;Wang N;Hu F;Luo Q;Shu H;Zhao F;Yao M;Fang J;Cong W;Qin W;Wang C
热休克蛋白27(Hsp27)是一种不依赖于ATP的分子伴侣，在应激条件下对癌细胞具有生存优势和耐药性。Hsp27在肝癌侵袭转移中的作用及其分子机制尚不清楚。本研究采用肝细胞癌组织芯片(n=167)研究Hsp27在肝细胞癌患者中的表达及其与预后的关系。Hsp27高表达的肝细胞癌患者预后不良。Hsp27的过表达导致了肝癌细胞的侵袭，而沉默Hsp27则减弱了肝癌细胞在体内外的侵袭和转移。我们发现Hsp27激活Akt信号通路，进而促进MMP2和ITGA7的表达，进而促进肝癌的转移。我们进一步观察到，在两种转移模型中，使用OGX-427靶向Hsp27明显抑制了肝癌的转移。这些结果表明，Hsp27是预测肝癌预后的有用因子，它通过Akt信号通路促进肝癌的转移。用OGX-427靶向Hsp27可能是一种有吸引力的抑制肝癌转移的治疗选择。
Heat shock protein 27 (Hsp27) is an ATP-independent molecular chaperone and confers survival advantages and resistance to cancer cells under stress conditions. The effects and molecular mechanisms of Hsp27 in HCC invasion and metastasis are still unclear. In this study, hepatocellular carcinoma (HCC) tissue array (n = 167) was used to investigate the expression and prognostic relevance of Hsp27 in HCC patients. HCC patients with high expression of Hsp27 exhibited poor prognosis. Overexpression of Hsp27 led to the forced invasion of HCC cells, whereas silencing Hsp27 attenuated invasion and metastasis of HCC cells in vitro and in vivo. We revealed that Hsp27 activated Akt signaling, which in turn promoted MMP2 and ITGA7 expression and HCC metastasis. We further observed that targeting Hsp27 using OGX-427 obviously suppressed HCC metastasis in two metastatic models. These findings indicate that Hsp27 is a useful predictive factor for prognosis of HCC and it facilitates HCC metastasis through Akt signaling. Targeting Hsp27 with OGX-427 may represent an attractive therapeutic option for suppressing HCC metastasis.