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• W2048753310 abstract "The molecular mechanism underlying metastasis of hepatocellular carcinoma (HCC) remains elusive. Here, we showed that matrix metalloproteinase (MMP) 7 and MMP26 levels are significantly higher in the resected HCC than in the adjacent healthy hepatic cells from the patients. Moreover, a strong correlation of the levels of MMP7 or MMP26 with the phosphorylated fibroblast growth factor receptor 2 (FGFR2) was detected. To prove a causal link between the activation of FGFR signaling pathway and expression of MMP7 and MMP26, we used two human HCC lines, HepG2 and HuH-7, to study the underlying molecular basis. We found that FGF1-induced FGFR2 phosphorylation in either line resulted in significant activation of MMP7 and MMP26 and consequently an increase in cancer invasiveness. Inhibition of FGFR2 phosphorylation in HCC abolished FGF1-stimulated MMP7 and MMP26 expression, suggesting that activation of the FGFR signaling pathway in HCC may promote cancer metastasis by inducing MMP7 and MMP26 expression. To define the signal transduction cascades downstream of FGFR2 activation for MMP7 and MMP26 activation, we applied specific inhibitors for phosphatidylinositol-3 kinase (PI3K), extracellular signal-related kinase/mitogen-activated protein kinase (ERK/MAPK), and Jun N-terminal kinase (JNK), respectively, to the FGF1-stimulated HCC cells. We found that only inhibition of JNK significantly decreased the activation of MMP26 in response to FGF1 stimulation, and only inhibition of PI3K significantly decreased the activation of MMP7 in response to FGF1 stimulation, suggesting that the activation of the FGFR2 signaling may activate PI3K to activate MMP7 and activate JNK to activate MMP26, in HCC. Our study thus highlights the FGFR2 signaling pathway and MMP7 and MMP26 as novel therapeutic targets for HCC." @default.
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• W2048753310 date "2014-08-05" @default.
• W2048753310 modified "2023-09-27" @default.
• W2048753310 title "Inhibition of fibroblast growth factor receptor signaling impairs metastasis of hepatocellular carcinoma" @default.
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• W2048753310 doi "https://doi.org/10.1007/s13277-014-2384-0" @default.
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