Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness

被引：105

作者：

Duxbury, MS ^{[1
]}

Ito, H ^{[1
]}

Zinner, MJ ^{[1
]}

Ashley, SW ^{[1
]}

Whang, EE ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 320卷 / 04期

关键词：

pancreatic; cancer adenocarcinoma; EphA2; tyrosine kinase; ephrin A1; invasion; focal adhesion kinase;

D O I：

10.1016/j.bbrc.2004.06.054

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Eph tyrosine kinases interact with ligands of the Ephrin family and have diverse cellular functions. EphA2 has been recognized to be an oncoprotein of importance in a range of cancers. Here, we examine the effect of EphA2 overexpression and ligation by chimeric Ephrin A1-Fc on the invasive phenotype of pancreatic adenocarcinoma cells. We show that EphA2 overexpression induces a FAK-dependent increase in MMP-2 expression and invasiveness. EphA2 ligation induces proteosomal degradation of EphA2, attenuates the invasive phenotype, and decreases both FAK phosphorylation and MMP-2 expression. EphA2 appears to represent a rational therapeutic target and ligation by Ephrin A1-Fc is one strategy to modulate levels of this oncoprotein. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：1096 / 1102

页数：7

共 42 条

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