title: Overexpression of c-Met increases the tumor invasion of human prostate LNCaP cancer cellsin vitroandin vivo.
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.
authors.affiliation: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Mingchuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Jiang
keywords: c-Met; epithelial-mesenchymal transition; invasive potency; prostate cancer