The nucleolar stress response at the centre of the malignant phenotype

The formation of malignancies is driven by a delicate sequence of events where failure to undergo effective apoptosis is a common denominator. A key player in apoptosis is the cellular stress response. Strikingly, the FUS and DDIT3 genes are involved in the cellular stress response and the FUS-DDIT3 fusion gene alone is capable of inducing myxoid liposarcoma (MLS). This provides a unique reductionist model for how stress-related pathways drive transformation in malignancy. In this proposal, we aim to elucidate how the FUS-DDIT3 fusion gene allows MLS tumour cell apoptosis evasion through hijacking ribosome biogenesis and function via stress-induced liquid-liquid phase separation.