Poster Presentation 28th Lorne Cancer Conference 2016

Investigating the role of Histidine metabolism in brain tumours in Drosophila melanogaster (#131)

Olivia Costas 1 , Francesca Froldi 1 , Louise Cheng 1
  1. Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

Cancer cells are known to undergo alterations in their metabolic requirements, including changes in amino acid metabolism. Current data concerning the metabolic utilization of amino acids in tumours is conflicting and inconclusive. To address the impact of Histidine metabolism on cancer growth, tumour models in Drosophila melanogaster were analysed. Nerfin-1 is a zinc finger transcription factor, required in post-mitotic neurons to maintain their differentiated state. It has been shown that nerfin-1 null brain tumours decreased growth upon dietary removal of Histidine. Therefore, we hypothesize that Histidine is an important metabolite of nerfin-1 null tumour growth, and additionally may be necessary for the growth of other genetically defined tumours. We aim to determine the mechanisms by which Histidine contributes to tumour size, and whether other tumours are susceptible to Histidine withdrawal. We utilize both dietary manipulations, and RNAi knockdown of two Histidine metabolic enzymes, 1-Histidine-N-methylstransferase (HNMT) and Histidine decarboxylase (HDC) to address how Histidine metabolism affects nerfin-1 null tumour growth. Immunohistochemistry and 3D image analysis is utilized to determine alterations within the cells and the cell populations. Upon knockdown of Histidine metabolic enzymes, nerfin-1 null tumours undergo decreased dedifferentiation, coupled with a decrease in cellular growth and a downregulation in Myc expression. However, not all tumours respond to manipulations in Histidine metabolism. We show that epithelial tumour types are not affected by Histidine metabolic inhibition, but brain tumours that arise from Notch activation are reduced.