Invited Speaker Oral 2nd Australian Cancer and Metabolism Meeting 2017

Metabolic reprogramming of neuronal dedifferentiation (#11)

Louise Cheng 1
  1. Growth regulation laboratory, Cancer research division, Peter MacCallum Cancer Centre, Melbourne , VIC, Australia

The effect of diet on tumour growth is hotly debated, but the mechanisms underlying the sensitivity of tumours to dietary manipulations remain poorly understood. To investigate this question, we utilised a chemically defined diet (CDD) to specifically withdraw a number of dietary components, and assess their contributions to tumour growth. Fruit flies carrying neural or epithelial tumour clones generated during development were subject to CDD missing essential amino acids during adult stages. Strikingly, dietary Histidine withdrawal and RNAis against Histadine metabolic enzymes effectively diminished the growth of a subset of neural tumours, without affecting proliferation of normal stem cell populations or other tumours. The sensitivity of tumours to Histidine manipulations is predicted by whether they arise via Myc-dependent cellular dedifferentiation, as tumours insensitive to Myc knockdown continue to growth under Histidine withdrawal. The metabolic vulnerabilities in amino acid metabolism we identify has the potential to inform the search of dietary intervention that specifically inhibit dedifferentiation in tumours without affecting normal cells.