Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
Cancer Discov. 2014 May;4(5):527-37. doi: 10.1158/2159-8290.CD-13-1005. Epub 2014 Apr 17.
In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.
在癌细胞中，核质转运机制经常被打乱，导致许多关键调节蛋白的定位错误和功能丧失。在这篇综述中，将阐明肿瘤细胞如何利用核转运机制促进癌变、细胞存活、耐药性和肿瘤进展的机制，特别关注核质输出蛋白的作用。还将讨论新一代核输出选择性抑制剂（XPO1 拮抗剂）的最新发展，以及这些新型抗癌药物如何使我们更接近于在临床上实施这一治疗策略。
