Dynamin2 downregulation delays EGFR endocytic trafficking and promotes EGFR signaling and invasion in hepatocellular carcinoma.
Dynamin2 downregulation delays EGFR endocytic trafficking and promotes EGFR signaling and invasion in hepatocellular carcinoma.
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Dynamin2 下调可延迟 EGFR 内吞运输并促进肝细胞癌中的 EGFR 信号传导和侵袭。
DOI：
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Ren Zhenggang
中科院分区：
文献类型：
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作者：
Gong Chaojie;Zhang Jubo;Zhang Lan;Wang Yingcong;Ma Hui;Wu Weizhong;Cui Jiefeng;Wang Yanhong;Ren Zhenggang
内吞失调被认为是癌症发展和进展的一个新特征。一个大的GTP酶动力蛋白2在受体酪氨酸激酶（RTK）的内吞作用中起着重要的作用。本研究旨在探讨其在肝细胞癌（HCC）转移中的作用及其机制。通过免疫组化评估HCC患者癌组织中的发动蛋白2表达，并使用单变量和多变量分析进行其对患者的预后意义。采用siRNA介导的基因沉默技术和Dynasore小分子抑制剂，体外研究其在肿瘤侵袭和转移中的作用。在Dynamin 2抑制后，通过Western印迹和免疫荧光分析评估HCC细胞系中EGFR的表达和EGFR下游信号转导ERK 1/2。我们的数据表明dynamin 2的低表达与侵袭特征和较短的总生存期密切相关。在肝癌细胞中抑制dynamin 2后，肝癌细胞的迁移、集落形成和侵袭显著增加。当dynamin 2被敲低或抑制时，EGFR的内化显著减少。此外，我们观察到dynamin 2调节EGF介导的EGFR下游Ras/ERK 1/2信号转导和p-ERK 1/2在细胞核中的积聚。结果表明，发动蛋白参与EGFR的内吞和肝癌转移的调节的可能机制。Dynamin 2通过促进EGFR内吞和下调ERK 1/2磷酸化抑制肝癌细胞的侵袭和转移。
Dysregulation of endocytosis was viewed as an emerging feature of cancer development and progression. A large GTPase dynamin2 plays a significant role in receptor tyrosine kinases (RTKs) endocytosis. The study was designed to investigate its roles in hepatocellular carcinoma (HCC) metastasis and its underlying mechanism. Dynamin2 expression in cancer tissues from HCC patients was assessed by immunohistochemistry and its prognostic significance for the patients was conducted using univariate and multivariate analysis. Its role in tumor invasion and metastasis was evaluated in vitro by gene silence using siRNA-mediated approach and the small molecule inhibitor of Dynasore. EGFR expression in HCC cell lines and EGFR downstream signaling ERK1/2 was evaluated by Western-blot and immunofluorescence analyses after Dynamin2 inhibition. Our data indicated that low expression of dynamin2 was well correlated with invasion characteristics and shorter overall survival. HCC cell migration, colony formation and invasion were significantly increased after the inhibition of dynamin2 in HCC cells. Internalization of EGFR was markedly reduced when dynamin2 was knock down or inhibition. In addition, we observed that dynamin2 regulated EGF mediated EGFR downstream Ras/ERK1/2 signaling and p-ERK1/2 accumulation in nucleus. The results demonstrate a possible mechanism of dynamin involved EGFR endocytosis and modulation of metastasis in HCC. Dynamin2 inhibits the invasion and metastasis of HCC cells by the promotion of EGFR endocytosis and downregulation of ERK1/2 phosphorylation.
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影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
3.6
作者：
Lee, Yoo-Young;Do, In-Gu;Bae, Duk-Soo
通讯作者：
Bae, Duk-Soo
影响因子：
64.8
作者：
OBAR, RA;COLLINS, CA;VALLEE, RB
通讯作者：
VALLEE, RB
DOI：
10.1073/pnas.0915123107
发表时间：
2010-03-30
影响因子：
11.1
作者：
Weller, Shaun G.;Capitani, Mirco;McNiven, Mark A.
通讯作者：
McNiven, Mark A.
影响因子：
8
作者：
Eppinga, R. D.;Krueger, E. W.;Weller, S. G.;Zhang, L.;Cao, H.;McNiven, M. A.
通讯作者：
McNiven, M. A.