Determining the molecular interface between nutrition, cell growth and tumourigenesis

SM Li1, O Zaytseva1, L Guo1, N Mitchell1, R Hannan2, L Quinn1 and LM Parsons1

  1. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Melbourne 3010, Australia
  2. Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra Australian Capital Territory 2600, Australia

Organ growth requires coordination of nutrient availability with the precise regulation of cell number and/or cell size. We have shown that the ‘nutrient sensing kinase’ (Salt Inducible Kinase 2, dSIK2) regulates cell growth/size in Drosophila and that it acts via the potent oncogene MYC. In Drosophila and mammals, SIK2 acts as a ‘fuel gauge’, monitoring cellular levels of ATP and glucose. When ATP or glucose levels fall (nutrient starvation), SIK2 promotes glucose synthesis to produce cellular energy. Thus, SIK2 activity is required to promote cell survival under conditions of metabolic stress. Intriguingly, the risk of specific cancers increases in patients with metabolic dysfunction including obesity and diabetes. However, the mechanisms that link diabetes, obesity and cancer remain poorly defined. Exciting studies, utilising a Drosophila cancer model, revealed that tumour cells were more aggressive in flies fed a high sugar diet. Strikingly, knockdown of dSIK2 in tumours of animals raised on a high sugar diet decreased tumour growth and prevented metastatic spread. We hypothesise, in a tumour setting, dSIK2 activity is required to overcome metabolic stress to promote cancer cell growth. Therefore, we aim to understand how the nutrient sensing kinase, dSIK2, regulates organ size in healthy tissues and how dSIK2 contributes to tumour pathogenesis.