Journal
NATURE
Volume 541, Issue 7637, Pages 417-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature20815
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Funding
- Research Council of Norway through its Centres of Excellence funding scheme [179571]
- Norwegian Cancer Society [PK01-2009-0386, 145517, 71043-PR-2006-0320]
- Southern and Eastern Regional Health Authority [2015016]
- Norwegian Research Council [196898, 214448]
- NIH [RO1 GM090150]
- EU grant from the Simon Fougner Hartmanns Foundation [609020, LP2014-2]
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As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy(1), a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial(2). Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model(3,4), 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.
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