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锚蛋白重复结构域17(ANKRD17)诱导促生存信号通路,在肝细胞癌发生过程中增强细胞侵袭和迁移能力。

ANKRD17 induces pro-survival signaling pathways that enhance cellular invasion and migration during hepatocellular carcinoma tumorigenesis.

作者信息

Keng Vincent W, Su Shan, Chui Elyse S T, To Jeffrey C, Zhang Yao-Jun, Li Xiao-Xiao

机构信息

The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China.

Department of Applied Biology and Chemical Technology, State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.

出版信息

iScience. 2025 Apr 17;28(5):112463. doi: 10.1016/j.isci.2025.112463. eCollection 2025 May 16.

Abstract

Metastasis is the primary cause of high mortality in patients with hepatocellular carcinoma (HCC) . A prior study identified ankyrin repeat domain 17 () as a key gene linked to HCC metastasis. Through reverse genetics, it was observed that mouse liver tumors overexpressing exhibited a higher tumor load and increased expression of endothelial-mesenchymal transition (EMT) markers. Similarly, overexpression in human liver cell lines resulted in an amplified cellular motility and invasion capability, whereas knockdown studies reversed this effect. Abnormal regulation of signaling pathways was linked to increased metastasis and survival in cells overexpressing . Notably, the pro-metastatic discoidin domain receptor tyrosine kinase 1 () gene was upregulated in these cells, and its suppression reduced motility and invasion without affecting AKT signaling. Clinically, higher expression correlated with aggressive HCC progression. These findings suggest that enhances metastatic progression in HCC by activating pro-metastatic and pro-survival pathways.

摘要

转移是肝细胞癌(HCC)患者高死亡率的主要原因。先前的一项研究确定锚蛋白重复结构域17(ANKRD17)是与HCC转移相关的关键基因。通过反向遗传学观察到,过表达ANKRD17的小鼠肝肿瘤表现出更高的肿瘤负荷以及内皮-间充质转化(EMT)标志物表达增加。同样,ANKRD17在人肝癌细胞系中的过表达导致细胞运动性和侵袭能力增强,而敲低实验则逆转了这种效应。信号通路的异常调节与过表达ANKRD17的细胞中转移增加和存活有关。值得注意的是,促转移的盘状结构域受体酪氨酸激酶1(DDR1)基因在这些细胞中上调,其抑制可降低运动性和侵袭能力,而不影响AKT信号传导。临床上,ANKRD17的高表达与侵袭性HCC进展相关。这些发现表明,ANKRD17通过激活促转移和促存活途径增强HCC的转移进程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1b9/12127597/d800c9298196/fx1.jpg

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