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

Maria Meehan, Royal College of Surgeons in Ireland
Laavanya Parthasarathi, Royal College of Surgeons in Ireland
Niamh Moran, Royal College of Surgeons in Ireland
Caroline A. Jefferies, Royal College of Surgeons in Ireland
Niamh Foley, Royal College of Surgeons in Ireland
Elisa Lazzari, Royal College of Surgeons in Ireland
Derek Murphy, Royal College of Surgeons in Ireland
Jacqueline Ryan, Royal College of Surgeons in Ireland
Berenice Ortiz, Memorial Sloan-Kettering Cancer Center, NY
Armida W M Fabius, Memorial Sloan-Kettering Cancer Center, NY
Timothy A. Chan, Memorial Sloan-Kettering Cancer Center, NY
Raymond L. Stallings, Royal College of Surgeons in Ireland

Document Type Article

This article is also available at http://www.molecular-cancer.com/content/11/1/6 or http://www.molecular-cancer.com/content/11/1/6

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.