Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

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dc.contributor.authorLi, J.
dc.contributor.authorGu, D.
dc.contributor.authorLee, SS-Y.
dc.contributor.authorSong, B.
dc.contributor.authorBandyopadhyay, S.
dc.contributor.authorChen, S.
dc.contributor.authorKonieczny, SF.
dc.contributor.authorRatliff, TL.
dc.contributor.authorLiu, X.
dc.contributor.authorXie, J.
dc.contributor.authorCheng, J-X.
dc.contributor.departmentDepartment of Pediatrics, IU School of Medicineen_US
dc.date.accessioned2017-06-13T20:07:49Z
dc.date.available2017-06-13T20:07:49Z
dc.date.issued2016-12-15
dc.description.abstractCancer 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_US
dc.identifier.citationLi, 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.2016.168en_US
dc.identifier.urihttps://hdl.handle.net/1805/13001
dc.language.isoen_USen_US
dc.publisherSpringerNatureen_US
dc.relation.isversionof10.1038/onc.2016.168en_US
dc.relation.journalOncogeneen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourcePMCen_US
dc.subjectCancer cellsen_US
dc.subjectGlucose metabolismen_US
dc.subjectAmino acid metabolismen_US
dc.subjectLipid metabolismen_US
dc.subjectCholesterol metabolismen_US
dc.subjectCancer metastasisen_US
dc.subjectPancreatic canceren_US
dc.subjectCholesterol esterificationen_US
dc.titleAbrogating cholesterol esterification suppresses growth and metastasis of pancreatic canceren_US
dc.typeArticleen_US
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