Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.
Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
Sci Rep. 2016 Oct 19;6:35609. doi: 10.1038/srep35609.
β-arrestins, including β-arrestin1 and β-arrestin2, are multifunctional adaptor proteins. β-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered β-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma (HCC) is not clear. We therefore examined the roles of β-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential. We demonstrated that β-arrestin2 level, but not β-arrestin1 level, decreased in conjunction with liver tumourigenesis in a mouse diethylnitrosamine-induced liver tumour model. Furthermore, β-arrestin2 expression was reduced in HCC tissues compared with noncancerous tissues in HCC patients. β-arrestin2 down-regulation in HCC was significantly associated with poor patient prognoses and aggressive pathologic features. In addition, our in vitro study showed that β-arrestin2 overexpression significantly reduced cell migration and invasion in cultured HCC cells. Furthermore, β-arrestin2 overexpression up-regulated E-cadherin expression and inhibited vimentin expression and Akt activation. These results suggest that β-arrestin2 down-regulation increases HCC cell migration and invasion ability. Low β-arrestin2 expression may be indicative of a poor prognosis or early cancer recurrence in patients who have undergone surgery for HCC.
β-arrestins，包括β-arrestin1 和 β-arrestin2，是多功能衔接蛋白。最近发现β-arrestins 在调节与恶性细胞功能相关的细胞内信号转导网络方面发挥新作用。许多癌症中都报道了β-arrestin 的表达改变，但在肝细胞癌 (HCC) 中的作用尚不清楚。因此，我们使用进行性 HCC 的动物模型、HCC 患者样本和具有逐步转移潜能的 HCC 细胞系来研究β-arrestins 在 HCC 中的作用。我们证明，在小鼠二乙基亚硝胺诱导的肝肿瘤模型中，β-arrestin2 水平而非β-arrestin1 水平随着肝肿瘤发生而降低。此外，与 HCC 患者的非癌组织相比，β-arrestin2 在 HCC 组织中的表达减少。β-arrestin2 在 HCC 中的下调与患者预后不良和侵袭性病理特征显著相关。此外，我们的体外研究表明，β-arrestin2 的过表达显著降低了培养的 HCC 细胞的迁移和侵袭能力。此外，β-arrestin2 的过表达上调了 E-钙黏蛋白的表达，并抑制了波形蛋白的表达和 Akt 的激活。这些结果表明，β-arrestin2 的下调增加了 HCC 细胞的迁移和侵袭能力。β-arrestin2 表达水平低可能表明接受 HCC 手术的患者预后不良或早期癌症复发。
