Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness
Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness
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DOI：
10.1016/j.bbrc.2004.06.054
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发表时间：
2004-08-06
影响因子：
3.1
通讯作者：
Whang, EE
中科院分区：
文献类型：
--
作者：
Duxbury, MS;Ito, H;Whang, EE
Eph酪氨酸激酶与肝配蛋白家族的配体相互作用，并具有不同的细胞功能。EphA 2已被认为是一系列癌症中重要的癌蛋白。在这里，我们研究EphA 2过表达和嵌合Ephrin A1-Fc连接对胰腺癌细胞侵袭表型的影响。我们发现EphA 2过表达诱导MMP-2表达和侵袭性的FAK依赖性增加。EphA 2连接诱导EphA 2的蛋白体降解，减弱侵袭性表型，并降低FAK磷酸化和MMP-2表达。EphA 2似乎代表了合理的治疗靶点，通过肝配蛋白A1-Fc连接是调节这种癌蛋白水平的一种策略。(C)2004爱思唯尔公司All rights reserved.
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.