Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

作者：Li J; Gu D; Lee S S Y; Song B; Bandyopadhyay S; Chen S; Konieczny S F; Ratliff T L; Liu X; Xie J^*; Cheng J X^*

来源：Oncogene, 2016, 35(50): 6378-6388.

DOI：10.1038/onc.2016.168

Cancer 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.

• 出版日期2016-12-15