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EGF promotes invasion by PANC-1 cells through Rac1/ROS-dependent secretion and activation of MMP-2.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Binker MG,Binker-Cosen AA,Richards D,Oliver B,Cosen-Binker LI

doi

10.1016/j.bbrc.2008.12.080

subject

Has Abstract

pub_date

2009-02-06 00:00:00

pages

445-50

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)02493-5

journal_volume

379

pub_type

杂志文章

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