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Int J Mol Sci. 2019 Mar 7;20(5). pii: E1170. doi: 10.3390/ijms20051170.

Dual-Specificity Phosphatases in Neuroblastoma Cell Growth and Differentiation.

Author information

1
Biomarkers in Cancer Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Bizkaia 48903, Spain. caroliten@gmail.com.
2
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital HF Radiumhospitalet, Oslo 0424, Norway. caroliten@gmail.com.
3
Department of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia 48903, Spain. laura.zaldumbideduenas@osakidetza.eus.
4
Biomarkers in Cancer Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Bizkaia 48903, Spain. olaia.aurtenetxesaez@osakidetza.eus.
5
Pediatric Oncology and Hematology, Cruces University Hospital, Barakaldo, Bizkaia 48903, Spain. ricardo.lopezalmaraz@osakidetza.eus.
6
Biomarkers in Cancer Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Bizkaia 48903, Spain. joseignacio.lopezfernandezdevillaverde@osakidetza.eus.
7
Department of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia 48903, Spain. joseignacio.lopezfernandezdevillaverde@osakidetza.eus.
8
Biomarkers in Cancer Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Bizkaia 48903, Spain. rpulidomurillo@gmail.com.
9
IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Spain. rpulidomurillo@gmail.com.

Abstract

Dual-specificity phosphatases (DUSPs) are important regulators of neuronal cell growth and differentiation by targeting proteins essential to neuronal survival in signaling pathways, among which the MAP kinases (MAPKs) stand out. DUSPs include the MAPK phosphatases (MKPs), a family of enzymes that directly dephosphorylate MAPKs, as well as the small-size atypical DUSPs, a group of low molecular-weight enzymes which display more heterogeneous substrate specificity. Neuroblastoma (NB) is a malignancy intimately associated with the course of neuronal and neuroendocrine cell differentiation, and constitutes the source of more common extracranial solid pediatric tumors. Here, we review the current knowledge on the involvement of MKPs and small-size atypical DUSPs in NB cell growth and differentiation, and discuss the potential of DUSPs as predictive biomarkers and therapeutic targets in human NB.

KEYWORDS:

MAP kinase phosphatases; MAP kinases; atypical dual-specificity phosphatases; dual-specificity phosphatases; neuroblastoma; neuronal differentiation

PMID:
30866462
DOI:
10.3390/ijms20051170
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