Microenvironmental autophagy promotes tumour growth

During early-stage tumour growth in Drosphila, tumour cells acquire necessary nutrients by triggering autophagy in surrounding cells in the tumour microenvironment. Induced autophagy promotes tumour progression Using a Drosophila model of tumorigenesis, Tor Erik Rusten and colleagues show that tumour cells under stress induce autophagy in their microenvironment, by oncogene and inflammatory signalling, as a way of generating nutrients for tumour growth and dissemination. These findings illustrate the importance of tumour-environmental crosstalk and shed light on the potential of systemic autophagy as a targetable process in cancer. 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.