Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

J. Li, D. Gu, S. S Y Lee, B. Song, S. Bandyopadhyay, Shaoxiong Chen, S. F. Konieczny, T. L. Ratliff, X. Liu, Jingwu Xie, J. X. Cheng

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6378-6388
Number of pages11
JournalOncogene
Volume35
Issue number50
DOIs
StatePublished - Dec 15 2016

Fingerprint

Esterification
Pancreatic Neoplasms
Cholesterol
Neoplasm Metastasis
Growth
Neoplasms
Endoplasmic Reticulum Stress
Cholesterol Esters
Small Interfering RNA
Apoptosis
Lipids
Amino Acids
Glucose
Cell Line
Survival
sterol O-acyltransferase 1
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Li, 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. https://doi.org/10.1038/onc.2016.168

Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. / Li, J.; Gu, D.; Lee, S. S Y; Song, B.; Bandyopadhyay, S.; Chen, Shaoxiong; Konieczny, S. F.; Ratliff, T. L.; Liu, X.; Xie, Jingwu; Cheng, J. X.

In: Oncogene, Vol. 35, No. 50, 15.12.2016, p. 6378-6388.

Research output: Contribution to journalArticle

Li, J, Gu, D, Lee, SSY, Song, B, Bandyopadhyay, S, Chen, S, Konieczny, SF, Ratliff, TL, Liu, X, Xie, J & Cheng, JX 2016, 'Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer', Oncogene, vol. 35, no. 50, pp. 6378-6388. https://doi.org/10.1038/onc.2016.168
Li, J. ; Gu, D. ; Lee, S. S Y ; Song, B. ; Bandyopadhyay, S. ; Chen, Shaoxiong ; Konieczny, S. F. ; Ratliff, T. L. ; Liu, X. ; Xie, Jingwu ; Cheng, J. X. / Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. In: Oncogene. 2016 ; Vol. 35, No. 50. pp. 6378-6388.
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