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2025;10 38.

AHR limits tumor growth and stem cell proliferation in the intestine.

Minghua Tsai, Jiawei Sun, Cyrille Alexandre, Michael Shapiro, Adrien Franchet, Ying Li, Alex P Gould, Jean-Paul Vincent, Brigitta Stockinger, Nicola Laura Diny
Author Information
  1. Minghua Tsai: The Francis Crick Institute, London, England, NW1 1AT, UK.
  2. Jiawei Sun: The Francis Crick Institute, London, England, NW1 1AT, UK.
  3. Cyrille Alexandre: The Francis Crick Institute, London, England, NW1 1AT, UK.
  4. Michael Shapiro: The Francis Crick Institute, London, England, NW1 1AT, UK.
  5. Adrien Franchet: The Francis Crick Institute, London, England, NW1 1AT, UK. ORCID
  6. Ying Li: The Francis Crick Institute, London, England, NW1 1AT, UK.
  7. Alex P Gould: The Francis Crick Institute, London, England, NW1 1AT, UK. ORCID
  8. Jean-Paul Vincent: The Francis Crick Institute, London, England, NW1 1AT, UK.
  9. Brigitta Stockinger: The Francis Crick Institute, London, England, NW1 1AT, UK.
  10. Nicola Laura Diny: The Francis Crick Institute, London, England, NW1 1AT, UK. ORCID
PMID: 40212817 DOI: 10.12688/wellcomeopenres.23515.2

Abstract

Background: The aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation in the intestinal epithelium. Spineless, the homolog of AHR, has only been studied in the context of development but not in the adult intestine.
Methods: The role of Spineless in the midgut was studied by overexpression or inactivation of Spineless in infection and tumour models and RNA sequencing of sorted midgut progenitor cells.
Results: We show that is upregulated in the adult intestinal epithelium after infection with ( . .). Spineless inactivation increased stem cell proliferation following infection-induced injury. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. In two tumour models, using either RNAi or constitutively active Yorkie, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. At the transcriptional level it reversed the gene expression changes induced in Yorkie tumours, counteracting cell proliferation and altered metabolism.
Conclusions: These findings demonstrate a new role for Spineless in the adult midgut and highlight the evolutionarily conserved functions of AHR/Spineless in the control of proliferation and differentiation of the intestinal epithelium.

Keywords

Drosophila aryl hydrocarbon receptor intestinal epithelium spineless tumour suppressor

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Word Cloud

Created with Highcharts 10.0.0SpinelessintestinaltumourproliferationepitheliumcellAHRgrowthadultmidgutinfectionstemarylhydrocarbonreceptordifferentiationstudiedintestineroleoverexpressioninactivationmodelsYorkieBackground:playsimportantroleshomeostasislimitingpromotinghomologcontextdevelopmentMethods:RNAsequencingsortedprogenitorcellsResults:showupregulatedincreasedfollowinginfection-inducedinjurylimitedreducedsurvivaltwousingeitherRNAiconstitutivelyactivesuppresseddoubledlifespantumour-bearingfliestranscriptionallevelreversedgeneexpressionchangesinducedtumourscounteractingalteredmetabolismConclusions:findingsdemonstratenewhighlightevolutionarilyconservedfunctionsAHR/SpinelesscontrollimitstumorDrosophilaspinelesssuppressor

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