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PCSK9 Protein Governs Liver-Versus-Lung Spread of Pancreatic Cancer

Regulating cholesterol access reveals how tumor cells adapt to distinct organs, offering new strategies to block metastasis.

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Overview

  • Scientists at UC San Francisco have discovered that the protein PCSK9 directs pancreatic cancer cells to metastasize preferentially to the liver or lungs.
  • Low PCSK9 levels drive tumor cells to scavenge external cholesterol abundant in the liver, while high levels enable internal cholesterol synthesis and oxidative protection needed for lung colonization.
  • Experimental overexpression of PCSK9 in liver-tropic cancer cells rerouted their spread to the lungs in preclinical models.
  • Published May 21 in Nature with funding from NIH, NSF and the American Association for Cancer Research, the study illuminates how cholesterol metabolism shapes metastatic organ choice.
  • Insights into PCSK9-mediated cholesterol acquisition point to a novel therapeutic target for combating metastatic pancreatic cancer.