Activation of the EGFR gene target EphA2 inhibits epidermal growth factor-induced cancer cell motility
Activation of the EGFR gene target EphA2 inhibits epidermal growth factor-induced cancer cell motility
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DOI：
10.1158/1541-7786.mcr-06-0321
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发表时间：
2007-03-01
影响因子：
5.2
通讯作者：
Poulsen, Hans Skovgaard
中科院分区：
文献类型：
--
作者：
Larsen, Alice Bjerregaard;Pedersen, Mikkel Wandahl;Poulsen, Hans Skovgaard
据报道，EphA2在许多肿瘤中过表达，并被认为在肿瘤转移和血管生成中发挥重要作用。我们发现激活的表皮生长因子受体(EGFR)和癌症特异性成分活性的EGFR III型缺失突变体(EGFRvIII)诱导哺乳动物细胞系，包括人类癌细胞系A431和HN5中EphA2的表达。这种调节部分依赖于丝裂原活化蛋白激酶/细胞外信号调节激酶的下游激活，并直接作用于EphA2启动子。此外，EGFR和EphA2都定位在质膜上，EphA2与激活的EGFR和EGFRvIII共沉淀。EphA2的配体激活和小干扰RNA敲除EphA2抑制了EGF诱导的高表达EGFR的人癌细胞的运动，表明EphA2在表达EGFR的癌细胞中具有功能作用。
EphA2 overexpression has been reported in many cancers and is believed to play an important role in tumor metastasis and angiogenesis. We show that the activated epidermal growth factor receptor (EGFR) and the cancer-specific constitutively active EGFR type III deletion mutant (EGFRvIII) induce the expression of EphA2 in mammalian cell lines, including the human cancer cell lines A431 and HN5. The regulation is partially dependent on downstream activation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase and is a direct effect on the EphA2 promoter. Furthermore, EGFR and EphA2 both localize to the plasma membrane and EphA2 coimmunoprecipitates with activated EGFR and EGFRvIII. Ligand activation of EphA2 and EphA2 knockdown by small interfering RNA inhibit EGF-induced cell motility of EGFR-overexpressing human cancer cells, indicating a functional role of EphA2 in EGFR-expressing cancer cells.