Cholesterol Metabolism Dictates Secondary Organ Colonization in Pancreatic Cancer

Major Finding: PCSK9 regulates cholesterol uptake and controls the trajectory of metastasis to secondary organs in pancreatic ductal adenocarcinoma (PDAC). Concept: Cholesterol uptake supports mTORC1-dependent growth in the liver, while cholesterol synthesis protects against oxidative stress to promote lung colonization.Impact: This study highlights the importance of metabolic adaptation in metastasis and suggests modulating different modes of cholesterol metabolism as a therapeutic strategy in PDAC.