Yesilkanal Ali Ekrem, Rosner Marsha Rich
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA.
Cancers (Basel). 2018 Sep 4;10(9):306. doi: 10.3390/cancers10090306.
Raf Kinase Inhibitory Protein (RKIP) is a highly conserved kinase inhibitor that functions as a metastasis suppressor in a variety of cancers. Since RKIP can reprogram tumor cells to a non-metastatic state by rewiring kinase networks, elucidating the mechanism by which RKIP acts not only reveals molecular mechanisms that regulate metastasis, but also represents an opportunity to target these signaling networks therapeutically. Although RKIP is often lost during metastatic progression, the mechanism by which this occurs in tumor cells is complex and not well understood. In this review, we summarize our current understanding of RKIP regulation in tumors and consider experimental and computational strategies for recovering or mimicking its function by targeting mediators of metastasis.
Raf激酶抑制蛋白(RKIP)是一种高度保守的激酶抑制剂,在多种癌症中作为转移抑制因子发挥作用。由于RKIP可通过重新连接激酶网络将肿瘤细胞重编程为非转移状态,阐明RKIP发挥作用的机制不仅能揭示调节转移的分子机制,还为通过治疗性靶向这些信号网络提供了契机。尽管RKIP在转移进展过程中常缺失,但肿瘤细胞中发生这种情况的机制复杂且尚未完全了解。在本综述中,我们总结了目前对肿瘤中RKIP调控的认识,并探讨通过靶向转移介质来恢复或模拟其功能的实验和计算策略。