Cholesteryl Ester Promotes Mammary Tumor Growth in MMTV-PyMT Mice and Activates Akt-mTOR Pathway in Tumor Cells.

Lengyun Wei,Shengmei Weng,Shenglong Zhu,Yongquan Chen,Xuyang Lu

doi:10.3390/biom11060853

Abstract

The association between intratumoral cholesteryl ester (CE) and tumor progression has been reported previously. The objective of our study was to investigate a causal effect of CE on mammary tumor progression. Using MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice and breast tumor cell MCF-7, we show that both exogenous and endogenous CE can increase mammary tumor growth, that CE upregulates the AKT/mTOR pathway, and that CE synthesis blockade suppresses this signaling pathway. Our data suggest that SOAT1, a sterol O-acyltransferase, may be a potential target for the treatment of breast cancer.

Highlights

IntroductionPromotes Mammary Tumor GrowthCholesterol esterification is a mechanism the body uses to store and transfer cholesterol and to avoid cellular toxicity of the excess of unesterified cholesterol [1,2]
Promotes Mammary Tumor GrowthCholesterol esterification is a mechanism the body uses to store and transfer cholesterol and to avoid cellular toxicity of the excess of unesterified cholesterol [1,2]
Some studies have demonstrated that intratumoral cholesteryl ester (CE) accumulation is intimately linked to the proliferation and aggressive potential of breast cancer and that the migration of MDA-MB-231 breast cancer cells depends on the availability of exogenous lipids and cholesterol esterification [3,8]

Summary

Introduction

Promotes Mammary Tumor GrowthCholesterol esterification is a mechanism the body uses to store and transfer cholesterol and to avoid cellular toxicity of the excess of unesterified cholesterol [1,2]. Some studies have demonstrated that intratumoral CE accumulation is intimately linked to the proliferation and aggressive potential of breast cancer and that the migration of MDA-MB-231 breast cancer cells depends on the availability of exogenous lipids and cholesterol esterification [3,8]. The abnormal accumulation of CEs may pose a threat to women’s health [9], few studies have investigated the causal effect of CE on breast cancer to date. The enzymes that catalyze the formation of CE from cholesterol and long-chain fatty acids in cells are sterol O-acyltransferases (SOAT1/2) [10,11]. Inhibition of cholesterol esterification via blocking SOAT1 has been reported to significantly reduce the proliferation of some solid tumor cells [13,14].

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