Hepatocytes promote liver metastasis of pancreatic cancer by providing serine.

Hepatocytes support pancreatic cancer liver metastasis by producing serine through a CXCL5-CXCR2-driven pathway, promoting tumor growth in the liver.

• Why it matters: Understanding how metastatic pancreatic cancer cells adapt to the liver microenvironment is crucial, especially since many rely on external serine due to PHGDH loss, yet the mechanisms in the liver niche remain unclear.
• What they did: The study examined exSer-dependent pancreatic ductal adenocarcinoma cells and their interaction with hepatocytes, using genetic and pharmacological methods to target the CXCL5-CXCR2-PI3K-AKT-FOXO3A axis in mice.
• The result: Disrupting this pathway or deleting key genes in hepatocytes significantly reduced liver metastasis and improved survival, especially with dietary serine restriction, highlighting potential therapeutic strategies.