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Nature. 2017 Jan 19;541(7637):417-420. doi: 10.1038/nature20815. Epub 2017 Jan 11.

Microenvironmental autophagy promotes tumour growth.

Author information

1
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
2
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, Norway.
3
Molecular Cancer Research Group, Institute of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromsø, Norway.
4
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
5
Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726 Hungary.
6
Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
7
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720-3200, USA.

Abstract

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.

PMID:
28077876
PMCID:
PMC5612666
DOI:
10.1038/nature20815
[Indexed for MEDLINE]
Free PMC Article

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