Phosphatase of regenerating liver: a novel target for cancer therapy

被引:56
作者
Campbell, Amanda M. [1 ,2 ]
Zhang, Zhong-Yin [1 ,2 ,3 ,4 ,5 ]
机构
[1] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA
[2] Purdue Univ, W Lafayette, IN 47907 USA
[3] Nankai Univ, Tianjin 300071, Peoples R China
[4] Upjohn Co, Kalamazoo, MI 49001 USA
[5] Univ Michigan, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
adhesion junctions; adhesion molecules; cell migration; colorectal cancer; de-trimerization; epithelial to mesenchymal transition; extracellular signal regulated kinases 1 and 2; filamentous actin dynamics; monoclonal antibody targeting; phosphatase and tensin homologue deleted on chromosome 10; phosphatase of regenerating liver; PI3K/Akt; receptor tyrosine kinases; small molecule inhibition; Src kinase; PROTEIN-TYROSINE PHOSPHATASES; SQUAMOUS-CELL CARCINOMA; MOUSE MELANOMA-CELLS; HUMAN GASTRIC-CANCER; COLORECTAL-CANCER; PRL-3; PHOSPHATASE; GENE-EXPRESSION; IN-VITRO; MONOCLONAL-ANTIBODIES; DOWN-REGULATION;
D O I
10.1517/14728222.2014.892926
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Introduction: 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. Areas covered: 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. Expert opinion: 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.
引用
收藏
页码:555 / 569
页数:15
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