Abstract 3124:SNAI2function in embryonal RMS

Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle and a key feature of the histology is muscle cells blocked in differentiation despite robust expression of diagnostic muscle differentiation factors MYOD1 and Myogenin. Thus, there are mechanisms operating in tumors that block myogenic differentiation. We previously defined roles in differentiation, self-renewal and growth for a NOTCH1/SNAI1/MEF2C pathway in Embryonal RMS, the major RMS subtype driven predominantly by Ras signaling. However, we observed that SNAI1 knockdown did not result in as robust differentiation as in NOTCH1 shRNA knockdown cells. We hypothesized that SNAI1 and SNAI2 function might be redundant in ERMS. Analysis of SNAI2 expression in primary tumors and cell lines finds that indeed SNAI2 is highly expressed in RMS and ERMS tumors typically express higher SNAI2 compared to SNAI1. To address SNAI2 function, we knocked down SNAI2 using 2 independent shRNAs and assessed effects on differentiation, self-renewal and growth in ERMS RD, SMS-CTR and JR1 cells. Knockdown of SNAI2 both in stable and transient experiments resulted in robust differentiation (10 fold increase) as assessed by differentiated myosin MF20 expression in RD, JR1 and SMS-CTR cells p Citation Format: Silvia Pomelo, Prethish Sreenivas, Berkley Gryder, Long Wang, Baxi Kunal, Nicole Hensch, Eleanor Chen, Peter Houghton, Rossella Rota, Javed Khan, Myron S. Ignatius. SNAI2 function in embryonal RMS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3124.