Li, J.Gu, D.Lee, SS-Y.Song, B.Bandyopadhyay, S.Chen, S.Konieczny, SF.Ratliff, TL.Liu, X.Xie, J.Cheng, J-X.2017-06-132017-06-132016-12-15Li, J., Gu, D., Lee, S. S.-Y., Song, B., Bandyopadhyay, S., Chen, S., … Cheng, J.-X. (2016). Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene, 35(50), 6378–6388. http://doi.org/10.1038/onc.2016.168https://hdl.handle.net/1805/13001Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role of cholesterol metabolism in cancer metastasis. By using label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of cholesterol esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesCancer cellsGlucose metabolismAmino acid metabolismLipid metabolismCholesterol metabolismCancer metastasisPancreatic cancerCholesterol esterificationArticle