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

作者：Meehan Maria; Parthasarathi Laavanya; Moran Niamh; Jefferies Caroline A; Foley Niamh; Lazzari Elisa; Murphy Derek; Ryan Jacqueline; Ortiz Berenice; Fabius Armida W M; Chan Timothy A; Stallings Raymond L^*

来源：Molecular Cancer, 2012, 11: 6.

DOI：10.1186/1476-4598-11-6

• PTPRD
• AURKA
• MYCN
• Neuroblastoma
• Tumor suppressor

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. %26lt;br%26gt;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%26apos;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. %26lt;br%26gt;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.

• 出版日期2012-2-5