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

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.

Tumor models in various Drosophila tissues

“…In the larval stage, the neuroblast undergoes stereotypic, self-renewing divisions to produce INPs (immature neural progenitors), which, upon maturation, undergo a few more rounds of asymmetric, self-renewing divisions to give rise to ganglion mother cells (GMCs) that subsequently generate postmitotic neurons or glia ( Bello et al, 2008 ). The disruption of cell-polarity and Notch pathway genes can potentially lead to tumorigenesis in the larval brain ( Froldi et al, 2019 ; Goh et al, 2013 ; Y. Song & Lu, 2011 ).…”

Role of Long Noncoding RNAs ZlMSTRG.11348 and UeMSTRG.02678 in Temperature-Dependent Culm Swelling in Zizania latifolia

“…For instance, restriction of serine and glycine drives the accumulation of toxic sphingolipids within tumours and reduces tumour cell growth [ 18 ]. Further, histidine deprivation reduce the growth of Drosophila tumour cells [ 54 ]. In order to examine whether lncRNAs are possibly involved in the amino acid mechanism at different temperatures, we identified genes involved in the amino acid metabolism from our RNA-seq data.…”

Misregulation of Drosophila Myc Disrupts Circadian Behavior and Metabolism

“…Histidine can be converted to histamine, which induces wakefulness in both mice and fruit flies (Oh et al, 2013; Parmentier et al, 2002; Thakkar, 2011). Interestingly, a recent study uncovered that the growth of dMyc-dependent neural dedifferentiation-derived clones in fruit flies is sensitive to histidine deprivation (Froldi et al, 2019). In that study, the mutant nerfin-1 clone (nerfin-1 is required for Drosophila neurons to maintain a differentiated state) that was generated in a Myc P0 (hypomorphic) heterozygous background failed to respond to dietary histidine supplementation, which can be rescued by dMyc overexpression.…”