Duxbury Mark S, Ito Hiromichi, Zinner Michael J, Ashley Stanley W, Whang Edward E
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Biochem Biophys Res Commun. 2004 Aug 6;320(4):1096-102. doi: 10.1016/j.bbrc.2004.06.054.
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.
Eph酪氨酸激酶与Ephrin家族的配体相互作用，并具有多种细胞功能。EphA2已被认为是多种癌症中一种重要的癌蛋白。在此，我们研究了EphA2过表达以及嵌合型Ephrin A1-Fc对胰腺腺癌细胞侵袭表型的影响。我们发现EphA2过表达会诱导FAK依赖的MMP-2表达增加和侵袭性增强。EphA2连接会诱导EphA2的蛋白酶体降解，减弱侵袭表型，并降低FAK磷酸化和MMP-2表达。EphA2似乎是一个合理的治疗靶点，通过Ephrin A1-Fc进行连接是调节这种癌蛋白水平的一种策略。
