Journal article
Histidine is selectively required for the growth of Myc-dependent dedifferentiation tumours in the Drosophila CNS
F Froldi, P Pachnis, M Szuperák, O Costas, T Fernando, AP Gould, LY Cheng
EMBO Journal | WILEY | Published : 2019
Abstract
Rewired metabolism of glutamine in cancer has been well documented, but less is known about other amino acids such as histidine. Here, we use Drosophila cancer models to show that decreasing the concentration of histidine in the diet strongly inhibits the growth of mutant clones induced by loss of Nerfin-1 or gain of Notch activity. In contrast, changes in dietary histidine have much less effect on the growth of wildtype neural stem cells and Prospero neural tumours. The reliance of tumours on dietary histidine and also on histidine decarboxylase (Hdc) depends upon their growth requirement for Myc. We demonstrate that Myc overexpression in nerfin-1 tumours is sufficient to switch their mode ..
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Awarded by Francis Crick Institute
Funding Acknowledgements
We are grateful to Paul Driscoll of the Francis Crick Institute Science Technology Platform for Metabolomics for advice and acknowledge Tom Frenkiel of the MRC Biomedical NMR Centre. We also thank Rita Sousa-Nunes and Andrew Bailey for critical reading of the manuscript. F.F., O.C., M.Z. and L.Y.C. are supported by NHMRC grant APP1044704 and Peter MacCallum Cancer Institute start-up funding. P.P., T.F. and A.P.G. are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001088), the UK Medical Research Council (FC001088) and the Wellcome Trust (FC001088), and previously by the UK Medical Research Council, National Institute for Medical Research (U117584237).