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Microenvironmental autophagy promotes tumour growth

Katheder, Nadja S.

Khezri, Rojyar

O'Farrell, Fergal

Schultz, Sebastian W

Jain, Ashish

Juhász, Gábor

Nature Publishing Group

2017

QH3015 Molecular biology / molekuláris biológia

RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkolĂłgia

As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment. Induction of autophagy is mediated by Drosophila tumour necrosis factor and interleukin-6-like signalling from metabolically stressed tumour cells, whereas tumour growth depends on active amino acid transport. We show that dormant growth-impaired tumours from autophagy-deficient animals reactivate tumorous growth when transplanted into autophagy-proficient hosts. We conclude that transformed cells engage surrounding normal cells as active and essential microenvironmental contributors to early tumour growth through nutrient-generating autophagy.

angol

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/73450/1/KathederNature.pdf

Katheder, Nadja S. and Khezri, Rojyar and O'Farrell, Fergal and Schultz, Sebastian W and Jain, Ashish and Juhász, Gábor (2017) Microenvironmental autophagy promotes tumour growth. NATURE, 541 (7637). pp. 417-420. ISSN 0028-0836

http://real.mtak.hu/73450/

http://doi.org/10.1038/nature20815

MTMT:3171474; doi:10.1038/nature20815