Novel Regulators of Checkpoint Adaptation in Fusion-Positive Rhabdomyosarcoma
Mentor: Corinne Linardic
Fusion-positive rhabdomyosarcoma, which is characterized by the PAX3-FOXO1 fusion oncoprotein, is a soft tissue sarcoma primarily impacting children and young adults. Decades of clinical trials have not produced novel therapies to improve the dismal survival rates for these patients. One feature of these tumors is their ability to undergo G2/M checkpoint adaptation, although the mechanisms allowing for tolerance of polyploidy and G2/M progression are poorly understood. We have demonstrated that transcriptional co-activators YAP and TAZ regulate progression through the G2/M checkpoint and may also regulate PAX3-FOXO1 activity. This proposal seeks to understand how YAP and TAZ functionally regulate the dynamic expression of PAX3-FOXO1 during G2, which may yield a vulnerability that could be exploited for new therapies.
