Abstract 827: Identification of the insulin-like growth factor 2 mRNA binding protein (IGF2BP1) as an important regulator of cIAP1 translation and apoptosis in rhabdomyosarcomas.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Rhabdomyosarcoma, a neoplasm characterized by undifferentiated myoblats-like cells, is the most common soft tissue sarcoma of childhood and represents 3-4% of all childhood cancers. IGF2BP1 is an oncofetal protein that was first identified in the rhabdomyosarcoma RD cell line and was shown to be overexpressed in a variety of cancers. Our group has previously identified IGF2BP1 as a potential translation modulator of the cellular inhibitor of apoptosis protein 1 (cIAP1), a key regulator of the NFκB signaling pathway and of caspase-8 mediated cell death in mammalian cells. In this study, we report that IGF2BP1 and cIAP1 expression is upregulated in a panel of rhabdomyosarcoma cell lines. We also show that IGF2BP1 is a positive regulator of cIAP1 translation, specifically through an internal ribosome entry site (IRES) mechanism. Finally, we report that altering the levels of cIAP1 in two rhabdomyosarcoma cell lines, RH36 and RH41, either by IGF2BP1 knock-down or by a Smac mimetic coumpound, sensitizes these cells to TNFα-mediated cell death. Our results identify IGF2BP1 and cIAP1 as important regulators of apoptosis in rhabdomyosarcomas. Citation Format: Mame Daro Faye, Tyson Graber, Stephanie Langlois, Kyle Cowan, Martin Holcik. Identification of the insulin-like growth factor 2 mRNA binding protein (IGF2BP1) as an important regulator of cIAP1 translation and apoptosis in rhabdomyosarcomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 827. doi:10.1158/1538-7445.AM2013-827