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Histidine is selectively required for the growth of Myc‐dependent dedifferentiation tumours in the Drosophila CNS
Author(s) -
Froldi Francesca,
Pachnis Panayotis,
Szuperák Milán,
Costas Olivia,
Fernando Tharindu,
Gould Alex P,
Cheng Louise Y
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899895
Subject(s) - biology , drosophila (subgenus) , histidine , drosophilidae , genetics , drosophila melanogaster , microbiology and biotechnology , cancer research , biochemistry , gene , amino acid
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 of growth from histidine/Hdc sensitive to resistant. This study suggests that perturbations in histidine metabolism selectively target neural tumours that grow via a dedifferentiation process involving large cell size increases driven by Myc.