Microenvironmental autophagy promotes tumour growth

Nadja S. Katheder, Rojyar Khezri, Fergal O'Farrell, Sebastian W. Schultz, Ashish Jain, Mohammed Kay O. Schink, Theodossis A. Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark, Tor Erik Rusten

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135 Citations (Scopus)

Abstract

As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy1, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial2. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model3,4, that noncellautonomous 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.

Original languageEnglish
Pages (from-to)417-420
Number of pages4
JournalNature
Volume541
Issue number7637
DOIs
Publication statusPublished - Jan 1 2017

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    Katheder, N. S., Khezri, R., O'Farrell, F., Schultz, S. W., Jain, A., Schink, M. K. O., Theodossiou, T. A., Johansen, T., Juhász, G., Bilder, D., Brech, A., Stenmark, H., & Rusten, T. E. (2017). Microenvironmental autophagy promotes tumour growth. Nature, 541(7637), 417-420. https://doi.org/10.1038/nature20815