Abstract 290: A Twist1 code of p53 inactivation

Twist proteins have been shown to contribute to cancer development and progression by impinging on different regulatory pathways, but their mechanism of action is poorly defined. By investigating the role of Twist in sarcomas, we identified an unprecedented mechanism of destabilization of p53. We show that Twist1 and MDM2 overexpression are mutually exclusive in these tumors and provide evidence that, by physically hindering p53 key phosphorylation, Twist1 facilitate MDM2:p53 complex formation and p53 degradation. This study suggests the existence of a Twist code of p53 inactivation in sarcomas and provides the proof of principle that targeting the Twist:p53 interaction may offer additional avenues for cancer treatment. 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 290. doi:1538-7445.AM2012-290