肝细胞生长因子受体/表皮生长因子受体交互作用与肿瘤耐药

Crosstalk between mesenchymal-epithelial transition factor and epithelial growth factor receptor in the development of resistance to anticancer drugs

肝细胞生长因子受体(mesenchymal-epithelial transition factor,MET)通路在肿瘤发生过程中具有重要作用,包括促进细胞增殖、抑制细胞凋亡、促进肿瘤血管生成、促进肿瘤细胞迁移及侵袭、转移等多个过程,涉及质膜、胞内共作用因子及下游效应蛋白的协同作用。体内、外实验证实,MET与表皮生长因子受体(epithelial growth factor receptor,EGFR)之间存在复杂的交互作用,两者共同参与细胞增殖、细胞运动及下游信号通路活化等多种细胞生物学事件,其中一些与肿瘤发生、进展密切相关。MET有可能通过"置换"EGFR活性而参与EGFR抑制剂的耐药发生。文中综述了肝细胞生长因子(hepatocyte growth factor,HGF)-MET和EGFR通路在肿瘤发生、发展过程中的重要作用,讨论了两者交互作用引起EGFR抑制剂耐药的可能机制,在此基础上提出联合使用EGFR和MET靶向抑制剂在克服EGFR抑制剂获得性耐药方面的应用前景。

The hepatocyte growth factor（HGF）-mesenchymal-epithelial transition factor（MET） pathway has been implicated in diverse cell events such as proliferation,inhibition of apoptosis,tumor angiogenesis,migration,invasiveness,and metastasis,all of which are driven through membrane and intracellular partners and several downstream effector proteins.The crosstalk between MET and epithelial growth factor receptor（EGFR） proteins plays a key role in multiple biological responses including tumor cell resistance to EGFR-targeting drugs,possibly via the activity substitution of EGFR by MET.This article presents an overview of recent data regarding HGF-MET and EGFR signaling cascades during carcinogenesis and a discussion on the rationale and prospects of the combinatorial blockage of both the pathways in cancer treatment.