Pancreatic cancer cells reprogram liver cells to boost serine production for metastasis
Researchers found that pancreatic ductal adenocarcinoma cells in mice signal liver hepatocytes to increase serine synthesis, aiding tumor growth.
Tumor cells rely on external serine
Nearly 40 percent of pancreatic ductal adenocarcinoma cases show a loss of the enzyme phosphoglycerate dehydrogenase. This loss makes the cancer cells dependent on exogenous serine found in their environment. The study notes that this metabolic vulnerability is common among disseminated tumour cells.
Liver cells are reprogrammed to help
ExSer-dependent cancer cells activate a CXCL5, CXCR2 axis to signal neighbouring hepatocytes for change. Activation of the CXCR2 receptor in liver cells triggers PI3K, AKT signalling pathways within those cells. This process causes FOXO3A to move into the cytoplasm and allows PHGDH transcription to increase.
Blocking the axis reduces metastasis
Inhibiting nodes within this specific metabolic axis or deleting relevant genes in mice reduced liver-metastasis burden. These interventions prolonged survival for the animals, especially when dietary serine was restricted. The findings confirm that hepatocyte-derived serine directly supports the outgrowth of these liver metastases.
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