Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan 250012, Shandong, China.
Cancer Biol Ther. 2010 Jan;9(2):79-87. doi: 10.4161/cbt.9.2.10280. Epub 2010 Jan 9.
Hepatocyte growth factor (HGF) plays an important role in stimulating tumor invasion and metastasis of tumor cells. However, the exact mechanisms of HGF regulation of cell invasion are largely unknown. In this study, we demonstrated that the MAPK specific inhibitor U0126 prevented the HGF-induced invasion of SKOV-3 cells. HGF stimulation of cell invasion and enhancement of MMP-9 expression were partially suppressed by TSP-1 overexpression. Furthermore, the MAPK signaling pathway is predominantly responsible for HGF-induced TSP-1 downregulation. We conclude that HGF is a potential downregulator of TSP-1, through MAPK signaling pathways, leading to the induction of MMP-9 expression and subsequent invasion of SKOV-3 cells. This study enhances our understanding of the mechanisms of signaling transduction in the HGF-induced invasion and progression of ovarian cancer.
肝细胞生长因子 (HGF) 在刺激肿瘤细胞的侵袭和转移方面发挥着重要作用。然而，HGF 调节细胞侵袭的确切机制在很大程度上尚不清楚。在本研究中，我们证明了 MAPK 特异性抑制剂 U0126 可阻止 HGF 诱导的 SKOV-3 细胞侵袭。TSP-1 的过表达部分抑制了 HGF 刺激的细胞侵袭和 MMP-9 表达的增强。此外，MAPK 信号通路主要负责 HGF 诱导的 TSP-1 下调。我们得出结论，HGF 是 TSP-1 的潜在下调因子，通过 MAPK 信号通路，导致 MMP-9 表达的诱导和随后的 SKOV-3 细胞侵袭。本研究增强了我们对 HGF 诱导的卵巢癌细胞侵袭和进展中信号转导机制的理解。
