Histidine is selectively required for the growth of Myc-dependent dedifferentiation tumours in the Drosophila CNS.

The EMBO Journal
Francesca FroldiLouise Y Cheng

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 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.

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Citations

Aug 28, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Edel Alvarez-OchoaLouise Y Cheng
Nov 14, 2019·Cell Reports·Annie L HsiehChi V Dang
May 16, 2020·Cancer Cell·Mylène Tajan, Karen H Vousden
Jul 3, 2021·International Journal of Molecular Sciences·Zheng-Hong WangDe-Ping Guo

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Methods Mentioned

BETA
dissection
Nuclear magnetic resonance
NMR
Profiler

Software Mentioned

Chenomx NMR Processor
Imaris
Volocity
Leica LAS
noesgppr1d
Chenomx NMR Profiler

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