Fig. 4.

Non-cell autonomous roles of autophagy in tumorigenesis. (A) Beyond work showing a central role for autophagy in promoting tumor cell survival via metabolite recycling, organelle homeostasis and tumor cell migration, data from mouse models have identified a non-cell autonomous role for autophagy in pancreatic stellate cells supporting PDAC tumor cells by providing amino acids (specifically alanine in published studies) while other work shows associated PSCs stimulate tumor cell migration by secreting IL-6 and other pro-migratory cytokines. In Drosophila, tumor cells released signals that promoted autophagy both in the tumor microenvironment and systemically. Autophagy also plays a critical role in anti-tumor immune responses. (B) Inhibition of autophagy systemically has a more marked inhibitory effect on repression of tumor growth than inhibition of autophagy in the tumor itself. This has been attributed to the role for autophagy in distant tissues, such as liver, muscle and fat, in providing amino acids, fatty acids and glucose to the tumor via the circulation.