Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness

Shuhua Yue, Junjie Li, Seung Young Lee, Hyeon Jeong Lee, Tian Shao, Bing Song, Liang Cheng, Timothy Masterson, Xiaoqi Liu, Timothy L. Ratliff, Ji Xin Cheng

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.

Original languageEnglish
Pages (from-to)393-406
Number of pages14
JournalCell Metabolism
Volume19
Issue number3
DOIs
StatePublished - Mar 4 2014

Fingerprint

Cholesterol Esters
Phosphatidylinositol 3-Kinases
Prostatic Neoplasms
Neoplasms
Cholesterol
Lipogenesis
Esterification
Lipid Metabolism
Heterografts
Prostate Cancer, Hereditary, 7
Neoplasm Metastasis
Growth

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. / Yue, Shuhua; Li, Junjie; Lee, Seung Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji Xin.

In: Cell Metabolism, Vol. 19, No. 3, 04.03.2014, p. 393-406.

Research output: Contribution to journalArticle

Yue, Shuhua ; Li, Junjie ; Lee, Seung Young ; Lee, Hyeon Jeong ; Shao, Tian ; Song, Bing ; Cheng, Liang ; Masterson, Timothy ; Liu, Xiaoqi ; Ratliff, Timothy L. ; Cheng, Ji Xin. / Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. In: Cell Metabolism. 2014 ; Vol. 19, No. 3. pp. 393-406.
@article{d603500082a749d5ac236bd7be63f7ff,
title = "Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness",
abstract = "Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.",
author = "Shuhua Yue and Junjie Li and Lee, {Seung Young} and Lee, {Hyeon Jeong} and Tian Shao and Bing Song and Liang Cheng and Timothy Masterson and Xiaoqi Liu and Ratliff, {Timothy L.} and Cheng, {Ji Xin}",
year = "2014",
month = "3",
day = "4",
doi = "10.1016/j.cmet.2014.01.019",
language = "English",
volume = "19",
pages = "393--406",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness

AU - Yue, Shuhua

AU - Li, Junjie

AU - Lee, Seung Young

AU - Lee, Hyeon Jeong

AU - Shao, Tian

AU - Song, Bing

AU - Cheng, Liang

AU - Masterson, Timothy

AU - Liu, Xiaoqi

AU - Ratliff, Timothy L.

AU - Cheng, Ji Xin

PY - 2014/3/4

Y1 - 2014/3/4

N2 - Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.

AB - Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.

UR - http://www.scopus.com/inward/record.url?scp=84895741045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895741045&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2014.01.019

DO - 10.1016/j.cmet.2014.01.019

M3 - Article

C2 - 24606897

AN - SCOPUS:84895741045

VL - 19

SP - 393

EP - 406

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 3

ER -