Phosphatase of Regenerating Liver: a Novel Target for Cancer Therapy

Overview

Journal Expert Opin Ther Targets

Publisher Informa Healthcare

Specialty Pharmacology

Date 2014 Mar 4

PMID 24579927

Citations 23

Authors

Amanda M Campbell

Zhong-Yin Zhang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation.

Chen H, Bai Y, Kobayashi M, Xiao S, Barajas S, Cai W Mol Cancer Res. 2023; 22(1):94-103.

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PRL2 inhibition elevates PTEN protein and ameliorates progression of acute myeloid leukemia.

Carlock C, Bai Y, Paige-Hood A, Li Q, Nguele Meke F, Zhang Z JCI Insight. 2023; 8(19).

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PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371.

Chen H, Bai Y, Kobayashi M, Xiao S, Cai W, Barajas S Blood. 2022; 141(3):244-259.

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A screen of FDA-approved drugs identifies inhibitors of protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3).

Rivas D, Dela Cerna M, Smith C, Sampathi S, Patty B, Lee D Sci Rep. 2021; 11(1):10302.

PMID: 33986418 PMC: 8119466. DOI: 10.1038/s41598-021-89668-5.

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