Hepatocyte growth factor enhances ovarian cancer cell invasion through down-regulation of thrombospondin-1
Hepatocyte growth factor enhances ovarian cancer cell invasion through down-regulation of thrombospondin-1
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DOI：
10.4161/cbt.9.2.10280
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发表时间：
2010-01
影响因子：
3.6
通讯作者：
Wei-dong Wei-Wei-dong-Wei-47748144;B. Kong;Qifeng Yang;X. Qu
中科院分区：
文献类型：
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作者：
Wei-dong Wei-Wei-dong-Wei-47748144;B. Kong;Qifeng Yang;X. Qu
肝细胞生长因子（HGF）在促进肿瘤细胞侵袭和转移中起着重要作用。然而，HGF调控细胞侵袭的确切机制在很大程度上是未知的。在这项研究中，我们证明了MAPK特异性抑制剂U0126可以阻止hgf诱导的SKOV-3细胞的侵袭。过表达TSP-1可部分抑制HGF对细胞侵袭的刺激和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的潜在下调者，通过MAPK信号通路，诱导MMP-9表达并随后侵袭SKOV-3细胞。本研究增强了我们对hgf诱导卵巢癌侵袭和发展的信号转导机制的理解。
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 down-regulation. We conclude that HGF is a potential down-regulator 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.