Katheder, N.S., Khezri, R., O'Farrell, F., Schultz, S.W., Jain, A., Rahman, M.M., Schink, 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.

FBrf0234568

Research paper

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.

PMC5612666 (PMC) (EuropePMC)