Microenvironmental autophagy promotes tumour growth

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, usi...

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Bibliographic Details
Published in:Nature (London) 2017-01, Vol.541 (7637), p.417-420
Main Authors: Katheder, Nadja S, Khezri, Rojyar, O'Farrell, Fergal, Schultz, Sebastian W, Jain, Ashish, Rahman, Mohammed M, Schink, Kay O, Theodossiou, Theodossis A, Johansen, Terje, Juhász, Gábor, Bilder, David, Brech, Andreas, Stenmark, Harald, Rusten, Tor Erik
Format: Article
Language:English
Subjects:
Amino Acids - metabolism
Analysis
Animals
Autophagy
Autophagy (Cytology)
Autophagy - drug effects
Autophagy - genetics
Biological Transport
Cell growth
Cell Proliferation
Disease Models, Animal
Drosophila
Drosophila melanogaster - cytology
Drosophila melanogaster - drug effects
Drosophila melanogaster - metabolism
Drosophila Proteins - deficiency
Drosophila Proteins - genetics
Female
Health aspects
Insects
Interleukin-6 - metabolism
Models, Biological
Neoplasm Invasiveness
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Reactive Oxygen Species - metabolism
Signal Transduction
Tumor Microenvironment
Tumor Necrosis Factor-alpha - metabolism
Tumor Suppressor Proteins - deficiency
Tumor Suppressor Proteins - genetics
Tumors
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature20815