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The antimicrobial peptide defensin cooperates with tumour necrosis factor to drive tumour cell death in Drosophila.

Jean-Philippe ParvyYachuan YuAnna DostalovaShu KondoAlina KurjanPhilippe BuletBruno LemaîtreMarcos VidalJulia B Cordero
Published in: eLife (2019)
Antimicrobial peptides (AMPs) are small cationic molecules best known as mediators of the innate defence against microbial infection. While in vitro and ex vivo evidence suggest AMPs' capacity to kill cancer cells, in vivo demonstration of an anti-tumour role of endogenous AMPs is lacking. Using a Drosophila model of tumourigenesis, we demonstrate a role for the AMP Defensin in the control of tumour progression. Our results reveal that Tumour Necrosis Factor mediates exposure of phosphatidylserine (PS), which makes tumour cells selectively sensitive to the action of Defensin remotely secreted from tracheal and fat tissues. Defensin binds tumour cells in PS-enriched areas, provoking cell death and tumour regression. Altogether, our results provide the first in vivo demonstration for a role of an endogenous AMP as an anti-cancer agent, as well as a mechanism that explains tumour cell sensitivity to the action of AMPs.
Keyphrases
  • cell death
  • induced apoptosis
  • immune response
  • adipose tissue
  • single cell
  • bone marrow
  • mesenchymal stem cells
  • genome wide
  • endoplasmic reticulum stress