Mutation in the Drosophila melanogaster adenosine receptor gene selectively decreases the mosaic hyperplastic epithelial outgrowth rates in wts or dco heterozygous flies

Roman Sidorov, Lucie Kucerova, I. Kiss, Michal Zurovec

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adenosine (Ado) is a ubiquitous metabolite that plays a prominent role as a paracrine homeostatic signal of metabolic imbalance within tissues. It quickly responds to various stress stimuli by adjusting energy metabolism and influencing cell growth and survival. Ado is also released by dead or dying cells and is present at significant concentrations in solid tumors. Ado signaling is mediated by Ado receptors (AdoR) and proteins modulating its concentration, including nucleoside transporters and Ado deaminases. We examined the impact of genetic manipulations of three Drosophila genes involved in Ado signaling on the incidence of somatic mosaic clones formed by the loss of heterozygosity (LOH) of tumor suppressor and marker genes. We show here that genetic manipulations with the AdoR, equilibrative nucleoside transporter 2 (Ent2), and Ado deaminase growth factor-A (Adgf-A) cause dramatic changes in the frequency of hyperplastic outgrowth clones formed by LOH of the warts (wts) tumor suppressor, while they have almost no effect on control yellow (y) clones. In addition, the effect of AdoR is dose-sensitive and its overexpression leads to the increase in wts hyperplastic epithelial outgrowth rates. Consistently, the frequency of mosaic hyperplastic outgrowth clones generated by the LOH of another tumor suppressor, discs overgrown (dco), belonging to the wts signaling pathway is also dependent on AdoR. Our results provide interesting insight into the maintenance of tissue homeostasis at a cellular level.

Original languageEnglish
Pages (from-to)95-105
Number of pages11
JournalPurinergic Signalling
Volume11
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Warts
Purinergic P1 Receptors
Drosophila melanogaster
Diptera
Adenosine
Loss of Heterozygosity
Clone Cells
Mutation
Adenosine Deaminase
Equilibrative-Nucleoside Transporter 2
Nucleoside Deaminases
Genes
Nucleoside Transport Proteins
Neoplasms
Tumor Biomarkers
Tumor Suppressor Genes
Energy Metabolism
Drosophila
Cell Survival
Intercellular Signaling Peptides and Proteins

Keywords

  • Adgf-A
  • Cell competition
  • Discs overgrown
  • Ent2
  • LATS1
  • Warts

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Mutation in the Drosophila melanogaster adenosine receptor gene selectively decreases the mosaic hyperplastic epithelial outgrowth rates in wts or dco heterozygous flies. / Sidorov, Roman; Kucerova, Lucie; Kiss, I.; Zurovec, Michal.

In: Purinergic Signalling, Vol. 11, No. 1, 2015, p. 95-105.

Research output: Contribution to journalArticle

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