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

Parvy, J.-P., Yu, Y., Dostalova, A., Kondo, S., Kurjan, A., Bulet, P., Lemaitre, B., Vidal, M. and Cordero, J. B. (2019) The antimicrobial peptide Defensin cooperates with tumour necrosis factor to drive tumour cell death in Drosophila. eLife, 8, e45061. (doi: 10.7554/eLife.45061) (PMID:31358113) (PMCID:PMC6667213)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cordero, Professor Julia and Yu, Dr Yachuan and Vidal, Dr Marcos and Parvy, Dr Jean-Philippe
Creator Roles:
Cordero, J.Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review and editing
Vidal, M.Conceptualization
Parvy, J.-P.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review and editing
Yu, Y.Formal analysis, Investigation
Authors: Parvy, J.-P., Yu, Y., Dostalova, A., Kondo, S., Kurjan, A., Bulet, P., Lemaitre, B., Vidal, M., and Cordero, J. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Published Online:30 July 2019
Copyright Holders:Copyright © 2019 Parvy et al.
First Published:First published in ELife 8:e45061
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
633021Regulation of stem cell function during tissue homeostasis and transformationJulia CorderoWellcome Trust (WELLCOTR)104103/Z/14/ZRI CANCER SCIENCES