Astrocytes are the most abundant cell in the central nervous system (CNS). Following injury to the nervous system, astrocytes respond through a repair process known as astrocyte activation. While the molecular mechanisms of astrocyte activation are not completely established, understanding the dynamic changes that occur in response to injury could help identify critical signaling pathways involved in the pathogenesis of brain tumors. To determine the mechanisms underlying astrocyte activation, including the initiating events and regulatory mediators of this process, we analyzed the molecular signaling changes after scratch injury of astrocytes. We discovered that the interruption and destabilization of cadherin-catenin complexes plays a critical role in the initiation and regulation of astrocyte activation. We further found that similar expression changes and signaling pathways are also featured in gliomas, but were found to exist in a dysregulated manner. Inhibition of β-catenin signaling was also found to diminish both the astrocyte response to injury and the malignant phenotype of gliomas. These findings provide a unique mechanism of normal astrocyte activation and shed light on the pathogenic mechanism of glioma, which may help to develop the diagnostic and therapeutic targets for gliomas.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4220. doi:1538-7445.AM2012-4220