Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions.

The phenomenon of how oncogenes and tumor-suppressor mutations can synergize to promote tumor fitness and cancer progression can be studied in relatively simple animal model systems such as Almost two decades after the landmark discovery of cooperative oncogenesis between oncogenic and the loss of the tumor suppressor in flies, this and other tumor models have provided new concepts and findings in cancer biology that has remarkable parallels and relevance to human cancer. Here we review findings using the tumor model and how it has contributed to our understanding of how these initial simple genetic insults cooperate within the tumor cell to set in motion the malignant transformation program leading to tumor growth through cell growth, cell survival and proliferation, dismantling of cell-cell interactions, degradation of basement membrane and spreading to other organs. Recent findings have demonstrated that cooperativity goes beyond cell intrinsic mechanisms as the tumor interacts with the immediate cells of the microenvironment, the immune system and systemic organs to eventually facilitate malignant progression.

Host autophagy mediates organ wasting and nutrient mobilization for tumor growth.

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.