EphA2在乳腺癌治疗耐药中作用的研究进展

Research progress on the contribution of EphA2 in breast cancer therapy resistance

促红细胞生成素诱导肝细胞受体(erythropoietin-producing hepatocyte receptor,Eph)是目前已知的受体型酪氨酸激酶(receptor tyrosine kinase,RTK)中最庞大的家族。该家族与经典RTK的不同之处在于其配体Ephrin也是一种膜定位分子。因此,Ephrin-Eph介导的信号传导依赖细胞与细胞间的直接接触。生理情况下,该信号系统在调控胚胎发育和维持内环境稳态中发挥重要作用。Ephrin-Eph信号系统失调与肿瘤发生和发展密切相关。研究提示,在所有的Eph家族成员中,EphA2与肿瘤的关系最为密切。EphA2表达上调能够增强乳腺癌细胞的增殖、存活、侵袭、耐药和血管生成等多种恶性生物学行为。EphA2在乳腺癌组织中表达增高与患者预后不良密切相关。近年研究发现,EphA2有望成为一个预测乳腺癌治疗效果的分子标志物,而且很有可能成为一个治疗乳腺癌的分子靶标。本文主要针对EphA2在乳腺癌治疗耐药中的作用进行综述。

Erythropoietin-producing hepatocyte(Eph)receptors are the largest family of the known receptor tyrosine kinases(RTK).The difference between this family and canonical RTKs is that their ligands(Ephrin)are membrane-bound molecules.Hence,Ephrin-Eph-mediated signal transduction relies on direct cell to cell contact.This signaling system plays an important role in regulating embryonic development and maintaining homeostasis under physiological conditions.The dysregulation of Ephrin-Eph signaling system is closely related to carcinogenesis and cancer progression.Studies have shown that among all Eph family members,EphA2 has the closest relationship with tumors.The increased expression of EphA2 can promote the proliferation,survival,migration,invasion,drug resistance,and angiogenesis of breast cancer cells.The increased expression of EphA2 in breast cancer tissues is closely related to poor prognosis in patients.Recently,EphA2 is expected to be a molecular marker for predicting the effect of breast cancer treatment,and thus,can serve as a promising therapeutic target for breast cancer therapy.This review summarized the latest research progress on the contribution of EphA2 in breast cancer therapy resistance.