Raf-1激酶与肿瘤治疗

自Raf激酶被证明为逆转录病毒致癌基因的产物以来,逐渐成为人们研究的热点。研究表明,Raf激酶既是Ras的效应物,又能作为ERK信号通路中的重要组分,成为活化的Ras和ERK之间的一个重要纽带。Ras-Raf-MEK-ERK信号通路参与了细胞增殖、分化和凋亡等生物学过程。作为这一信号通路上的节点蛋白,Raf激酶在肿瘤发生过程中起着关键作用。Raf家族成员Raf-1（cRaf）在调控细胞运动和凋亡过程中发挥关键作用,它既可以通过抑制促凋亡激酶ASK1和MST2活性来抑制细胞凋亡,也可以通过激活Rok-α的活性来促进细胞迁移。该文主要综述了Raf-1激酶的调控机制及其在肿瘤发生过程中的作用,同时也总结了以Raf-1为靶点的肿瘤治疗的最新进展。

Raf-1 Kinase and Tumor Therapy

Since Raf kinases were identified as products of retroviroal oncogenes, the Raf kineses have been intensively studied. Raf kinases are not only the bona fide effectors of the Ras, but also activators of the typi- cal ERK signaling pathway, which provide an important link between Ras and ERK. Ras-Raf-MEK-ERK signaling pathway is involved in many biological process including cell proliferation, differentiation and apoptosis. As a node of the Ras-Raf-MEK-ERK signaling pathway, Raf kinases play a crucial role in tumorgensis. Raf-1, a key member of Raf family, regulates cell motility by controlling the activity of Rok-α, and apoptosis by suppressing the activity of the proapoptosis kinases, ASK1 and MST2. In this review, we described the regulation of Raf-1 kinase and its role in the tumorgensis. We also summarized the latest development in tumor therapy targeting Raf-1.