Abstract
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.
Highlights
Introduction cMet is a transmembrane tyrosine kinase receptor that is phosphorylated and activated upon the binding of its ligand
The paracrine signaling pathway is activated by HGF secretion by stromal cells, whereas the autocrine signaling pathway is initiated by HGF that is generated from cancer cells
These results demonstrated that an LNCaP cell line with stable c‐Met overexpression had been constructed and this was termed the LNCaP‐Met cell line
Summary
Introduction cMet is a transmembrane tyrosine kinase receptor that is phosphorylated and activated upon the binding of its ligand. A dysfunctional HGF/c‐Met axis has been implicated in the development, invasion and angiogenesis of cancers [6], and an increasing number of studies have revealed the specific mechanism [7,8]. Overexpression of c‐Met occurs via paracrine and autocrine stimulation of HGF, which in turn stimulates cancer cell progression. The paracrine signaling pathway is activated by HGF secretion by stromal cells, whereas the autocrine signaling pathway is initiated by HGF that is generated from cancer cells. Previous studies have shown that certain signaling pathways mediate increased cancer progression as result of the HGF/c‐Met axis, typically the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase signaling pathways [10,11,12,13]
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