Overexpression of c-Met increases the tumor invasion of human prostate LNCaP cancer cells in vitro and in vivo.
Overexpression of c-Met increases the tumor invasion of human prostate LNCaP cancer cells in vitro and in vivo.
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DOI：
10.3892/ol.2014.2390
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发表时间：
2014-10
期刊：
影响因子：
2.9
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Han Y;Luo Y;Zhao J;Li M;Jiang Y
c-Met是一种跨膜酪氨酸激酶受体，可被肝细胞生长因子激活，作为上皮间质转化（epithelial-mesenchymal transition， EMT）的诱导剂，调节相关下游基因表达。这一过程对正常和病理条件下的细胞迁移至关重要。本研究探讨c-Met在前列腺癌EMT过程中的作用。首先，使用EMT和c-Met阴性的LNCaP前列腺癌细胞构建c-Met稳定表达细胞系。在转染细胞中鉴定c-Met后，采用western blot方法检测EMT、磷脂酰肌醇3-激酶（PI3K）和细胞外信号调节激酶途径生物标志物的变化。采用MTT法、软琼脂法、Transwell法和异种移植法研究c-Met对LNCaP细胞增殖、迁移和致瘤性的影响。本研究结果显示，LNCaP-Met细胞中E-cadherin下调，vimentin上调。结果表明，与LNCaP和LNCaP- pcdna3.1细胞相比，c-Met增强了细胞的增殖、迁移和致瘤能力。此外，这些emt样的变化是通过PI3K和丝裂原激活的蛋白激酶信号通路介导的。目前的研究清楚地表明c-Met在前列腺癌EMT发展中的关键作用。c- met靶向治疗可能是提高前列腺癌患者生存率的有效辅助治疗。
c-Met is a transmembrane tyrosine kinase receptor that may be activated by hepatocyte growth factor, an inducer of epithelial-mesenchymal transition (EMT), to regulate the associated downstream gene expression. This process is critical to cell migration in normal and pathological conditions. In the present study, the function of c-Met in the process of EMT was investigated in prostate cancer. Initially, a c-Met stable expression cell line was constructed using EMT- and c-Met-negative LNCaP prostate cancer cells. Following the identification of c-Met in the transfected cells, the changes in EMT, phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase pathway biomarkers were determined by western blot analysis. MTT, soft agar and Transwell assays, and xenograft studies were used to investigate the effects of c-Met on the proliferation, migration and tumorigenicity of LNCaP cells. The results of the present study revealed downregulation of E-cadherin and upregulation of vimentin in LNCaP-Met cells. The results demonstrated that c-Met enhanced proliferation, migration and tumorigenicity capacity when compared with LNCaP and LNCaP-pcDNA3.1 cells. Furthermore, these EMT-like changes were mediated via the PI3K and mitogen-activated protein kinase signaling pathways. The present study clearly demonstrates a crucial function for c-Met in EMT development in prostate cancer. c-Met-targeted treatment may be an effective adjuvant therapy for improving survival rates in patients with prostate cancer.
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影响因子：
3.7
作者：
Matsuoka J;Yashiro M;Doi Y;Fuyuhiro Y;Kato Y;Shinto O;Noda S;Kashiwagi S;Aomatsu N;Hirakawa T;Hasegawa T;Shimizu K;Shimizu T;Miwa A;Yamada N;Sawada T;Hirakawa K
通讯作者：
Hirakawa K
影响因子：
14.5
作者：
Leopold PL;Vincent J;Wang H
通讯作者：
Wang H
DOI：
10.1016/j.ijrobp.2012.06.025
发表时间：
2012-11-15
影响因子：
7
作者：
Li, Bo;Torossian, Artour;Lu, Bo
通讯作者：
Lu, Bo
影响因子：
7.5
作者：
Lamouille, Samy;Subramanyam, Deepa;Blelloch, Robert;Derynck, Rik
通讯作者：
Derynck, Rik
影响因子：
19
作者：
Birchmeier, C;Gherardi, E
通讯作者：
Gherardi, E