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

Molecular Cancer

Research

Derek Murphy¹  Elisa Lazzari²  Caroline A Jefferies²  Niamh Moran²  Jacqueline Ryan³  Niamh Foley³  Maria Meehan³  Laavanya Parthasarathi³  Raymond L Stallings³  Timothy A Chan⁴  Berenice Ortiz⁴  Armida W M Fabius⁴ 

[1] Centre for Human Proteomics, Royal College of Surgeons in Ireland, Dublin 2, Dublin, Ireland;Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Dublin, Ireland;Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Dublin, Ireland;National Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Dublin, Ireland;Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10065, New York, NY, USA;

关键词: PTPRD;    AURKA;    MYCN;    Neuroblastoma;    Tumor suppressor;   

DOI  :  10.1186/1476-4598-11-6

 received in 2011-09-07, accepted in 2012-02-05,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundProtein 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.ResultsAs 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.ConclusionsPTPRD 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.

【 授权许可】

Unknown   
© Meehan et al; BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. 2012. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.