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. 2017 Mar 3;7:28. doi: 10.3389/fonc.2017.00028

Figure 2.

Figure 2

Overview of the molecular pathways involved in autophagy and its impact on pancreatic cancer metabolism. Constitutive nuclear import of MiT/TFE proteins by importin-8 (IPO8) upregulates the autophagic-lysosomal machinery in pancreatic ductal adenocarcinoma (PDAC) (11). Autophagy fuels the TCA cycle by amino acid production, shifting the usage of glucose from glycolysis to Ser/Gly biosynthesis (67). This mechanism is further strengthened by pancreatic stellate cells (PSCs) secreting alanine upon autophagy stimulation by unknown PDAC factors (15). Furthermore, the necessity for palmitate feeding oxidative phosphorylation is upregulated in PDAC. Citrate, produced during the TCA cycle, is used for fatty acid biosynthesis, leading to lipid droplet formation and microlipophagy (67). This process, together with the macropinocytotic uptake of extracellular proteins, amplifies the autophagic system in PDAC (11, 67). Arrows and names in bold mark an upregulated pathway in PDAC.