E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.
E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.
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发表时间：
1999-09
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通讯作者：
N. Zantek;Minoudokht Azimi;M. Fedor-Chaiken;Bingcheng Wang;R. Brackenbury;M. Kinch
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作者：
N. Zantek;Minoudokht Azimi;M. Fedor-Chaiken;Bingcheng Wang;R. Brackenbury;M. Kinch
EphA2 是受体酪氨酸激酶 Eph 家族的成员，人们越来越认识到该家族在疾病和发育中发挥着关键作用。我们在此报告 E-钙粘蛋白对 EphA2 的调节。在非肿瘤性上皮细胞中，EphA2 被酪氨酸磷酸化并定位于细胞与细胞接触的部位。这些特性需要 E-钙粘蛋白的正确表达和功能。在缺乏E-钙粘蛋白的乳腺癌细胞中，EphA2的磷酸酪氨酸含量降低，并且EphA2重新分布到膜皱褶中。转移细胞中 E-钙粘蛋白的表达恢复了 EphA2 磷酸化和定位的更正常模式。 EphA2 的激活，无论是通过 E-钙粘蛋白表达还是抗体介导的聚集，都会减少细胞与细胞外基质的粘附和细胞生长。总而言之，这表明 EphA2 功能依赖于 E-钙粘蛋白，并表明 E-钙粘蛋白功能的丧失可能通过对 EphA2 的影响来改变肿瘤细胞的生长和粘附。
EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development. We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.