Fig. 1
From: Fountain of youth of pancreatic cancer cells: the extracellular matrix
In PDAC tumor (light pink region), upon nutrient limitation, PDAC cells degrade collagen, which is produced by cancer-associated fibroblasts (CAFs) in the ECM, take up collagen fragments along with other proteins like albumin through macropinocytosis, and take up free proline either using the same process or through membrane transporters (SLC). Internalized vesicles fuse with lysosomes where collagen and albumin are degraded into free proline and free amino acids, all released in the cytosol. Proline is either incorporated into protein biomass or catabolized to fuel the tricarboxylic acid (TCA) cycle to promote PDAC cell survival and tumor growth. In liver metastasis (dark pink region) we can suspect the same metabolic process (shown by dark grey dotted arrows) as in primary PDAC for nutrient supply of growing metastatic niches. In breast cancer-derived lung metastases (blue region), proline catabolism supplies metastatic cells with adenosine triphosphate (ATP) to support their growth. MMP matrix metalloprotease; SLC solute carrier family
