The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma.
The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma.
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Notch1表达在肝内胆管癌迁移中的作用
DOI：
10.1186/1471-2407-13-244
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发表时间：
2013-05-20
期刊：
影响因子：
3.8
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zhou Q;Wang Y;Peng B;Liang L;Li J
Notch信号是组织发育的重要途径，在许多组织中参与肿瘤的发生；然而，Notch信号在肝内胆管癌（ICC）中的作用尚不清楚。在这项研究中，我们评估了Notch1在ICC中的表达及其对细胞迁移的影响。采用多种细胞和分子方法，包括基因转染、siRNA转染、RT-PCR、Western blotting、Rac激活试验和免疫荧光。我们发现Notch1在ICC组织和细胞系中上调。Notch1在胶质瘤细胞中的外源性表达增加了胶质瘤细胞的迁移和侵袭能力。同样，抑制Notch1表达使Rac1失活并抑制ICC细胞迁移。Notch1过表达诱导ICC细胞上皮-间质转化（EMT）表型，包括α-SMA和Vimentin表达增强，E-cadherin表达缺失，形态学改变和细胞骨架重组。Notch1可能通过引起上皮-间质转化和激活Rac1在ICC中诱导迁移效应，可作为ICC患者新的诊断和治疗靶点。
Notch signaling, a critical pathway for tissue development, contributes to tumorigenesis in many tissues; however, the roles of Notch signaling in Intrahepatic Cholangiocarcinoma (ICC) remains unclear. In this study, we evaluated the expression and effects of Notch1 on cell migration in ICC. Multiple cellular and molecular approaches were performed including gene transfection, siRNA transfection, RT-PCR, Western blotting, Rac activation assays and immunofluorescence. We found that Notch1 was up-regulated in ICC tissues and cell lines. The exogenous expression of Notch1 in glioma cells increased their migratory and invasive capacity. Similarly, the suppression of Notch1 expression inactivated Rac1 and inhibited ICC cell migration. Notch1 over expression induced an Epithelial-to-mesenchymal transition (EMT) phenotype that included enhanced expression of α-SMA and Vimentin, loss of E-cadherin expression, morphological changes and cytoskeletal reorganization in ICC cells. Notch1 may induce a migratory effect in ICC by causing an epithelial-mesenchymal transition and activating Rac1 and could serve as a novel diagnostic and therapeutic target in patients with ICC.
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缺氧会增强乳腺癌中的 Notch 信号传导，导致 E-钙粘蛋白表达减少，细胞迁移和侵袭增加。
影响因子：
8.8
作者：
Chen, J.;Imanaka, N.;Chen, J.;Griffin, J. D.
通讯作者：
Griffin, J. D.
影响因子：
3.7
作者：
Rao, PK;Dorsch, M;McCarthy, S
通讯作者：
McCarthy, S
影响因子：
2.7
作者：
Yoneya, T;Tahara, T;Nishikawa, M
通讯作者：
Nishikawa, M
影响因子：
25.7
作者：
Shaib, YH;Davila, JA;El-Serag, HB
通讯作者：
El-Serag, HB
影响因子：
16
作者：
Mumm, JS;Schroeter, EH;Kopan, R
通讯作者：
Kopan, R