Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway.
Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway.
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DOI：
10.1111/cas.13247
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发表时间：
2017-06
期刊：
影响因子：
5.7
通讯作者：
Wu D
中科院分区：
文献类型：
--
作者：
Chen P;Lei L;Wang J;Zou X;Zhang D;Deng L;Wu D
Talin 1是一种衔接蛋白，其将整合素缀合至细胞骨架并调节整合素和粘着斑信号传导。几项研究发现，Talin 1在几种肿瘤类型中过表达，并促进肿瘤进展。然而，Talin 1在肝细胞癌（HCC）进展中的明确作用仍不清楚，其功能机制仍不清楚。在这项研究中，我们发现Talin 1的表达从正常肝组织到肝硬化、肝增生、相应的邻近非肿瘤、原发性HCC和最终转移灶呈逐渐降低的趋势，表明Talin 1可能与HCC的开始到进展相关。与邻近非肿瘤组织相比，Talin 1在HCC组织中显著下调，并且低Talin 1表达与HCC进展和预后不良相关。此外，Talin 1敲低诱导上皮-间充质转化，并促进SK-Hep-1细胞和HepG 2细胞的迁移和侵袭。从机制上讲，我们发现ERK通路负责Talin 1敲低在HCC细胞中的这些促进作用。Talin 1基因敲低对上皮-间质转化、迁移和侵袭的促进作用可被特异性ERK 1/2抑制剂U 0126逆转。综上所述，我们的研究结果表明，Talin 1可能作为肝癌的肿瘤抑制因子和肝癌患者的潜在预后生物标志物。
Talin1 is an adaptor protein that conjugates integrins to the cytoskeleton and regulates integrins and focal adhesion signaling. Several studies have found that Talin1 is overexpressed in several tumor types and promotes tumor progression. However, the explicit role of Talin1 in hepatocellular carcinoma (HCC) progression is still unclear and its functional mechanism remains largely unknown. In this study, we showed a trend of gradually decreasing expression of Talin1 from normal liver tissues to hepatocirrhosis, liver hyperplasia, the corresponding adjacent non‐tumor, primary HCC, and eventually metastatic foci, indicating that Talin1 may correlate with HCC initiation to progression. Talin1 was significantly downregulated in HCC tissues compared with adjacent non‐tumor tissues and low Talin1 expression was associated with HCC progression and poor prognosis. Furthermore, Talin1 knockdown induced epithelial–mesenchymal transition and promoted migration and invasion in SK‐Hep‐1 cells and HepG2 cells. Mechanistically, we found that the ERK pathway was responsible for these promoting effects of Talin1 knockdown in HCC cells. The promoting effects of Talin1 knockdown on epithelial–mesenchymal transition, migration, and invasion were reversed by U0126, a specific ERK1/2 inhibitor. Taken together, our results suggested that Talin1 might serve as a tumor suppressor in HCC and a potential prognostic biomarker for HCC patients.