Fig. 2: The various roles of autophagy in pancreatic cancer.

The roles of autophagy in pancreatic tumour cells as well as in the components of the tumour microenvironment are depicted (red arrows indicate activation, blue bars indicate inhibition of cellular processes). Autophagy is activated by multiple cues in pancreatic cancer cells: increased autophagy gene expression upon transactivation by members of the MiTF/TFE3 transcription factor family, but also as a response to external stressors such as cytotoxic drugs, radiation, hypoxia, nutrient deprivation. Autophagy fuels the increased metabolism of tumour cells by providing energy and building blocks to help sustain proliferation. Cytokine secretion by cancer cells instruct normal stromal cells in the tumour microenvironment to release amino-acids such as alanine in the vicinity of tumour cells which provide additional nutritional support to proliferating cancer cells. Autophagy also plays a role in the maturation and maintenance of T cells as well as in antigen presentation by macrophages and other antigen-presenting cells.