title: Hepatocyte growth factor increases the invasive potential of PC-3 human prostate cancer cells via an ERK/MAPK and Zeb-1 signaling pathway.
abstract: Hepatocyte growth factor (HGF) has been implicated in epithelial-mesenchymal transition (EMT) in numerous types of cancer. However, to the best of our knowledge, there has been no previous evidence that HGF has a role in prostate cancer. The present study aimed to investigate the effect of HGF on EMT and invasive potential, as well as the underlying molecular mechanisms, in a human prostate cancer cell line. Therefore, PC-3 cells were treated with various concentrations of HGF for varying durations. EMT-associated proteins, including E-cadherin and vimentin, were examined by western blot analysis. The effects of HGF on cell proliferation, migration, invasion and tumorigenicity were assessed using MTT, wound-healing, Transwell and soft-agar assays. Subsequently, the role of c-Met in the mediation of EMT-like changes was investigated using reverse transcription-polymerase chain reaction, western blot analysis and gene knockdown by small interfering RNA. Finally, western blot analysis was used to quantify the expression of a downstream transcription factor and extracellular signal-related kinase/mitogen activated protein kinase (ERK/MAPK) signaling pathway proteins. The results indicated that treatment with HGF induced EMT-like changes and enhanced the invasive potential of PC-3 cells. There was an increase in the expression of ERK, phosphorylated-ERK and zinc finger E-box binding homeobox-1 (Zeb-1), suggesting that EMT-like changes may be mediated through the ERK/MAPK and Zeb-1 signaling pathway. Furthermore, HGF-mediated EMT-like changes were associated with c-Met activation, and these changes were able to be blocked by c-Met knockdown. The present study demonstrated that HGF-induced EMT increased the invasive potential of PC-3 human prostate cancer cells through activating the ERK/MAPK and Zeb-1 signaling pathway.
authors: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yili
authors: Y
authors: Han
authors: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yong
authors: Y
authors: Luo
authors: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yongxing
authors: Y
authors: Wang
authors: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yatong
authors: Y
authors: Chen
authors: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Mingchuan
authors: M
authors: Li
authors: Department of Urology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yongguang
authors: Y
authors: Jiang
keywords: epithelial-mesenchymal transition; extracellular signal-related kinase/mitogen activated protein kinase signaling pathway; hepatocyte growth factor; prostate cancer; zinc finger E-box binding homeobox