Microenvironmental autophagy promotes tumour growth

Article

关键词: CELL POLARITY;    ONCOGENIC RAS;    DROSOPHILA;    MAINTENANCE;    PROGRESSION;    OVERGROWTH;    ACTIVATION;    EXPRESSION;    INVASION;    SCRIBBLE;   

DOI  :  10.1038/nature20815

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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