We aim to determine how complex signalling pathways are integrated into transcriptional networks to pattern cell growth and division during development, and also maintain tissue homeostasis in adult animals. One core regulator of growth and division is the MYC oncoprotein, a potent transcriptional activator of the cell growth networks driving cancer initiation and progression. Increased abundance of MYC is sufficient to drive cancer, but the networks controlling MYC expression in malignancy are still nebulous. Using a combination of Drosophila and mammalian models we have demonstrated that the ssDNA/RNA binding proteins, the FUBP1 activator and FIR repressor, integrate cellular signaling inputs and act antagonistically to modulate MYC transcription. Not surprisingly, dysregulation of the FUBP1/FIR axis is linked with a wide variety of cancers, eg. kidney, breast, liver, lung, bladder, prostate, gastrointestinal and brain.

In the context of cancer, proper organisation of the cellular microenvironment will be essential for preventing tumour initiation and/or progression. However, this area of cancer biology has remained enigmatic, largely due to the difficulty in tracing interactions between human tumours and their niche using mammalian models. More than 2 decades of research in Drosophila have documented the capacity of the supporting cellular microenvironment or “niche” to orchestrate renewal and differentiation of neighbouring stem cell populations. I will present recent data demonstrating depletion of the FIR ortholog, specifically from the Drosophila ovarian stem cell niche, generates germline tumours independently of MYC function.