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Pediatric Brain Cancer Medulloblastoma

Identification of AZIN-1 as a key regulator of brain tumor aggressiveness

Potential use of AZIN-1 as a diagnostic and prognostic biomarker

AZIN1 is a cell cycle regulator upregulated in a variety of cancers. AZIN1 overexpression leads to a more aggressive tumor phenotype by binding to – and inhibiting – its target, antizyme.  Normally, antizyme serves as an anti-tumor regulatory agent by facilitating ubiquitin-independent degradation of several growth promoting proteins.c-Myc plays a critical role in medulloblastoma, the most common malignant brain tumor in children. Medulloblastoma is subdivided based on particular molecular features, in which c-Myc amplification is one of the most important molecular characters of groups 3 and 4 of medulloblastoma, associated with the most aggressive subtypes, metastasis, and poor prognosis.

In research, I have established that overexpression of AZIN1 in medulloblastoma cell lines induces the phenotypically aggressive features of increased invasion, migration and proliferation.  These in vitro data are corroborated with in vivo clinical specimens demonstrating that AZIN1 is highly expressed in medulloblastoma tissues. I also find that AZIN1 expression directly correlates with Myc staining in medulloblastoma patient samples, reinforcing our mechanistic hypothesis in a clinical setting. Furthermore, I show that AZIN1 exhibits potential utility as a biomarker.  AZIN1 concentration is higher in the cerebral spinal fluid (CSF) of medulloblastoma patients relative to matched controls and urinary AZIN1 concentrations reproducibly decrease after surgical removal of the tumor. Together, my data strongly indicate a significant role for AZIN1 in medulloblastoma development and suggest it may have immediate clinical application as both a biomarker and a novel therapeutic target.

Selected Publications:

In process…