During tumor growth—when nutrient and anabolic demands are high—autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling. Ras-driven tumors additionally invoke non-autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well-characterized malignant tumor model in Drosophila melanogaster. Micro-computed X-ray tomography and metabolic profiling reveal that Ras^V12; scrib^−/− tumors grow 10-fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, -motility, -feeding, and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth.

中文翻译：

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宿主自噬介导肿瘤生长的器官消耗和营养动员

在肿瘤生长过程中——当营养和合成代谢需求很高时——自噬通过溶酶体细胞器的周转和营养循环来支持肿瘤的代谢和生长。Ras 驱动的肿瘤另外在微环境中调用非自主自噬来支持肿瘤生长，部分是通过氨基酸的转移。在这里，我们使用在黑腹果蝇中充分表征的恶性肿瘤模型，揭示了自噬在介导全身器官消耗和肿瘤生长的营养动员中的第三个关键作用。微型计算机 X 射线断层扫描和代谢分析显示Ras ^V12 ; 脚本^-/-肿瘤体积增长 10 倍，而全身器官萎缩伴随进行性肌肉萎缩、体重下降、运动、进食和最终死亡。发现组织消瘦是由自噬介导的，并导致宿主将氨基酸和糖类调动到循环中。自然丰度碳 13 追踪表明，随着消瘦的进展，肿瘤生物量越来越多地来自宿主组织作为营养来源。我们得出结论，宿主自噬介导用于肿瘤生长的器官消耗和营养动员。