TY - JOUR
T1 - Keratinocyte growth factor/fibroblast growth factor-7-regulated cell migration and invasion through activation of NF-κB transcription factors
AU - Niu, Jiangong
AU - Chang, Zhe
AU - Peng, Bailu
AU - Xia, Qianghua
AU - Lu, Weiqin
AU - Huang, Peng
AU - Tsao, Ming Sound
AU - Chiao, Paul J.
PY - 2007/3/2
Y1 - 2007/3/2
N2 - Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7) is a paracrine- and epithelium-specific growth factor produced by cells of mesenchymal origin. It acts exclusively through FGF-7 receptor (FGFR2/IIIb), which is expressed predominantly by epithelial cells, but not by fibroblasts, suggesting that it might function as a paracrine mediator of mesenchymal-epithelial interactions. KGF/FGF-7 plays an essential role in the growth of epithelial cells and is frequently overexpressed in cancers of epithelial origin such as pancreatic cancer, switching paracrine stimulation of KGF/FGF-7 to an autocrine loop. Less is known, however, about the signaling pathways by which KGF/FGF-7 regulates the response of epithelial cells. To delineate the signaling pathways activated by KGF/FGF-7 and examine cellular response to KGF/ FGF-7 stimulation, we performed functional analysis of KGF/ FGF-7 action. In this report, we show that KGF/FGF-7 activated nuclear factor κB (NF-κB), which in turn induced expression of VEGF, MMP-9, and urokinase-type plasminogen activator and increased migration and invasion of KGF/FGF-7-stimulated human pancreatic ductal epithelial cells. Expression of phosphorylation-defective IκBα(IκBαS32A,S36A), which blocked NF-κB activation, inhibited KGF/FGF-7-induced gene expression and cell migration and invasion. Our results demonstrate for the first time that KGF/FGF-7 induces NF-κB activation and that NF-κB plays an essential role in regulation of KGF/FGF-7-inducible gene expression and KGF/FGF-7-initiated cellular responses. Thus, these findings identify one signaling pathway for KGF/FGF-7-regulated cell migration and invasion and suggest that paracrine sources of KGF/FGF-7 are one of the malignancy- contributing factors from tumor stroma.
AB - Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7) is a paracrine- and epithelium-specific growth factor produced by cells of mesenchymal origin. It acts exclusively through FGF-7 receptor (FGFR2/IIIb), which is expressed predominantly by epithelial cells, but not by fibroblasts, suggesting that it might function as a paracrine mediator of mesenchymal-epithelial interactions. KGF/FGF-7 plays an essential role in the growth of epithelial cells and is frequently overexpressed in cancers of epithelial origin such as pancreatic cancer, switching paracrine stimulation of KGF/FGF-7 to an autocrine loop. Less is known, however, about the signaling pathways by which KGF/FGF-7 regulates the response of epithelial cells. To delineate the signaling pathways activated by KGF/FGF-7 and examine cellular response to KGF/ FGF-7 stimulation, we performed functional analysis of KGF/ FGF-7 action. In this report, we show that KGF/FGF-7 activated nuclear factor κB (NF-κB), which in turn induced expression of VEGF, MMP-9, and urokinase-type plasminogen activator and increased migration and invasion of KGF/FGF-7-stimulated human pancreatic ductal epithelial cells. Expression of phosphorylation-defective IκBα(IκBαS32A,S36A), which blocked NF-κB activation, inhibited KGF/FGF-7-induced gene expression and cell migration and invasion. Our results demonstrate for the first time that KGF/FGF-7 induces NF-κB activation and that NF-κB plays an essential role in regulation of KGF/FGF-7-inducible gene expression and KGF/FGF-7-initiated cellular responses. Thus, these findings identify one signaling pathway for KGF/FGF-7-regulated cell migration and invasion and suggest that paracrine sources of KGF/FGF-7 are one of the malignancy- contributing factors from tumor stroma.
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U2 - 10.1074/jbc.M606878200
DO - 10.1074/jbc.M606878200
M3 - Article
C2 - 17200110
AN - SCOPUS:34250352380
SN - 0021-9258
VL - 282
SP - 6001
EP - 6011
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -