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ARK5通过调节上皮-间质转化促进肝癌细胞的侵袭和迁移。

ARK5 promotes invasion and migration in hepatocellular carcinoma cells by regulating epithelial-mesenchymal transition.

作者信息

Ye Zhiyu, Chen Xudong, Chen Xiaogang

机构信息

Department of Hernia and Hepatobiliary Surgery, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):1511-1516. doi: 10.3892/ol.2017.7453. Epub 2017 Nov 21.

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. The highly invasive nature of HCC leads to poor prognosis in patients with malignant HCC. AMPK-related protein kinase 5 (ARK5) is a key mediator of migratory activity in human cancer cells. However, the role of ARK5 in invasion and metastasis of HCC cells remains unclear. The present study attempted to determine whether ARK5 is involved in invasion and migration via regulation of epithelial-mesenchymal transition (EMT). Wound healing and Transwell Matrigel invasion assays were utilized to detect the ability of the epithelial Huh7 and mesenchymal SNU387 HCC cells to migrate and invade. Next, the expression of ARK5 and EMT markers, E-cadherin and vimentin, were examined by western blot analysis. Inhibition of ARK5 was able to significantly reduce the ability HCC cells to invade and metastasize. Furthermore, the knockdown of ARK5 was able to reverse the process of EMT in HCC cells. These data suggested that ARK5 may serve an important role in regulating EMT in HCC cells. Taken together, these findings indicate that ARK5 is a potential molecular target for the development of novel HCC therapeutics, which focus on cell invasion and EMT regulation.

摘要

肝细胞癌(HCC)是全球癌症相关死亡的第三大主要原因。HCC的高侵袭性导致恶性HCC患者预后不良。AMPK相关蛋白激酶5(ARK5)是人类癌细胞迁移活性的关键介质。然而,ARK5在HCC细胞侵袭和转移中的作用仍不清楚。本研究试图确定ARK5是否通过调节上皮-间质转化(EMT)参与侵袭和迁移。采用伤口愈合和Transwell Matrigel侵袭试验检测上皮性Huh7和间质性SNU387 HCC细胞的迁移和侵袭能力。接下来,通过蛋白质印迹分析检测ARK5和EMT标志物E-钙黏蛋白和波形蛋白的表达。抑制ARK5能够显著降低HCC细胞的侵袭和转移能力。此外,敲低ARK5能够逆转HCC细胞中的EMT过程。这些数据表明ARK5可能在调节HCC细胞的EMT中起重要作用。综上所述,这些发现表明ARK5是开发新型HCC治疗药物的潜在分子靶点,这些药物专注于细胞侵袭和EMT调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a32d/5774381/85d8705ab269/ol-15-02-1511-g00.jpg

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