Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10766426 | Biochemical and Biophysical Research Communications | 2009 | 6 Pages |
Abstract
Cancer metastasis involves tumor cells invading the surrounding tissue. Remodeling of tissue barriers depends on the ability of tumor cells to degrade the surrounding collagen matrix and then migrate through the matrix defects. Epidermal growth factor (EGF) has been shown to regulate tumor cell invasion through activation of matrix metalloproteinase-2 (MMP-2) in various tumor cell types. In the present study, we investigated the role of MMP-2 and the signaling pathway involved in EGF-promoted invasion by human pancreatic cancer cells PANC-1. Using specific inhibitors, we found that EGF stimulation of these tumor cells induced secretion and activation of the collagenase MMP-2, which was required for EGF-stimulated basement membrane degradation and cell invasion. Our results also indicate that signaling events downstream of EGF receptor involved PI3K- and Src-dependent activation of Rac1, which mediated the NADPH-generated reactive oxygen species responsible for MMP-2 secretion and activation.
Keywords
EGFRMatrix metalloproteinase-2 (MMP-2)Panc-1 cellsPP2Rac1NADPHEGFMMPPI3KDPIROSCancer invasionDiphenyleneiodoniumEpidermal growth factor (EGF)epidermal growth factorPhosphatidylinositol 3-kinasematrix metalloproteinasenicotinamide adenine dinucleotide phosphatepyrazolopyrimidineReactive oxygen species (ROS)Reactive oxygen speciesEGF receptor
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Authors
Marcelo G. Binker, Andres A. Binker-Cosen, Daniel Richards, Brenda Oliver, Laura I. Cosen-Binker,