Indiana University School of Medicine, Department of Biochemistry and Molecular Biology , John D. Van Nuys Medical Science Building, Room 4053A, 635 Barnhill Drive, Indianapolis, IN 46202-5126 , USA.
Expert Opin Ther Targets. 2014 May;18(5):555-69. doi: 10.1517/14728222.2014.892926. Epub 2014 Mar 1.
Phosphatases of regenerating livers (PRLs) are novel oncogenes that interact with many well-established cell signaling pathways that are misregulated in cancer, and are known to drive cancer metastasis when overexpressed.
This review covers basic information of the discovery and characteristics of the PRL family. We also report findings on the role of PRL in cancer, cell functions and cell signaling. Furthermore, PRL's suitability as a novel drug target is discussed along with current methods being developed to facilitate PRL inhibition.
PRLs show great potential as novel drug targets for anticancer therapeutics. Studies indicate that PRL can perturb major cancer pathways such as Src/ERK1/2 and PTEN/PI3K/Akt. Upregulation of PRLs has also been shown to drive cancer metastasis. However, in order to fully realize its therapeutic potential, a deeper understanding of the function of PRL in normal tissue and in cancer must be obtained. Novel and integrated biochemical, chemical, biological, and genetic approaches will be needed to identify PRL substrate(s) and to provide proof-of-concept data on the druggability of the PRL phosphatases.
肝再生磷酸酶(PRLs)是新型癌基因,与许多在癌症中失调的已确立的细胞信号通路相互作用,并且已知在过表达时会促进癌症转移。
本综述涵盖了 PRL 家族的发现和特征的基本信息。我们还报告了 PRL 在癌症、细胞功能和细胞信号转导中的作用的发现。此外,还讨论了 PRL 作为新型药物靶标的适用性,以及正在开发的促进 PRL 抑制的当前方法。
PRLs 作为癌症治疗的新型药物靶标具有很大的潜力。研究表明,PRL 可以扰乱 Src/ERK1/2 和 PTEN/PI3K/Akt 等主要癌症途径。上调 PRLs 也已被证明可驱动癌症转移。然而,为了充分实现其治疗潜力,必须更深入地了解 PRL 在正常组织和癌症中的功能。需要新的和综合的生化、化学、生物学和遗传方法来鉴定 PRL 的底物,并提供 PRL 磷酸酶的可药性的概念验证数据。