AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma.
AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma.
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AXL 受体激酶是肝细胞癌中 YAP 依赖性致癌功能的介质
DOI：
10.1038/onc.2010.504
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发表时间：
2011-03-10
期刊：
影响因子：
8
通讯作者：
Luk, J. M.
中科院分区：
文献类型：
--
作者：
Xu, M. Z.;Chan, S. W.;Liu, A. M.;Wong, K. F.;Fan, S. T.;Chen, J.;Poon, R. T.;Zender, L.;Lowe, S. W.;Hong, W.;Luk, J. M.
Yes相关蛋白（雅普）是Hippo信号通路的下游效应子，其控制器官扩张和组织发育。我们最近确定了YAP 1癌基因在人肝细胞癌（HCC）中的致瘤潜力和临床意义。本研究旨在明确雅普在肝癌中的致瘤特性并阐明相关的下游信号传导机制。在一项功能获得性研究中，我们证明了雅普在永生化的非致瘤性肝细胞系MIHA中异位表达的增加赋予了致瘤性和转移性潜能，如（1）增强的细胞活力、非贴壁依赖性生长、迁移和侵袭的能力;（2）异种移植小鼠模型中的肿瘤形成;（3）肝癌标志物甲胎蛋白的诱导和丝裂原活化蛋白激酶的激活。此外，我们已经确定了AXL，受体酪氨酸激酶，作为一个关键的下游目标，驱动YAP依赖性致癌功能。RNAi介导的AXL表达的敲低降低了表达YAP的MIHA细胞和原代HCC细胞系增殖和侵袭的能力。这些结果表明，AXL是一个介导的YAP依赖的致癌活动，并暗示它作为一个潜在的治疗肝癌的目标。
Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion;(2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.
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影响因子：
4.8
作者：
Demarchi, F;Verardo, R;Schneider, C
通讯作者：
Schneider, C
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
DOI：
10.1152/ajpheart.00020.2004
发表时间：
2004-09-01
影响因子：
4.8
作者：
Hasanbasic, I;Cuerquis, J;Blostein, MD
通讯作者：
Blostein, MD
TAZ 促进细胞增殖和上皮间质转化，并受 hippo 通路抑制
影响因子：
5.3
作者：
Lei, Qun-Ying;Zhang, Heng;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang
影响因子：
6.4
作者：
CRAVEN, RJ;XU, LH;CANCE, WG
通讯作者：
CANCE, WG