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Open Access Highly Accessed Research

Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

Maria Meehan12, Laavanya Parthasarathi12, Niamh Moran1, Caroline A Jefferies1, Niamh Foley12, Elisa Lazzari1, Derek Murphy3, Jacqueline Ryan12, Berenice Ortiz4, Armida W M Fabius4, Timothy A Chan4 and Raymond L Stallings12*

Author Affiliations

1 Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Dublin, Ireland

2 National Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Dublin, Ireland

3 Centre for Human Proteomics, Royal College of Surgeons in Ireland, Dublin 2, Dublin, Ireland

4 Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

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Molecular Cancer 2012, 11:6  doi:10.1186/1476-4598-11-6

Published: 5 February 2012

Abstract

Background

Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown.

Results

As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma.

Conclusions

PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

Keywords:
PTPRD; AURKA; MYCN; Neuroblastoma; Tumor suppressor