LMS Seminar- Dr Daniel Murphy
Dangerous Liaisons between MYC and NUAK1
MYC is one of the most frequently de-regulated oncogenes across a spectrum of human cancers. My lab seeks to identify opportunities to selectively kill cancer cells based on elevated MYC. Synthetic lethal screening identified the AMPK-related kinase NUAK1 as selectively required to support cell viability when MYC is overexpressed. Initial data suggested a specific role for NUAK1 in maintaining ATP homeostasis. More recently, we have linked NUAK1 directly to the Oxidative stress pathway and shown that NUAK1 is required for efficient activation of the anti-oxidant master regulatory transcription factor NRF2. Suppression of NUAK1 thus incapacitates the oxidative stress response, exposing tumour cells to toxic levels of reactive Oxygen species. The therapeutic potential of exploiting this intrinsic vulnerability for cancer therapy will be discussed.