Loss of FBP1 by Snail-Mediated Repression Provides Metabolic Advantages in Basal-like Breast Cancer

被引：701

作者：

Dong, Chenfang ^{[1
,5
]}

Yuan, Tingting ^{[1
,5
]}

Wu, Yadi ^{[2
,5
]}

Wang, Yifan ^{[1
,5
]}

Fan, Teresa W. M. ^{[6
,7
]}

Miriyala, Sumitra ^{[4
,5
]}

Lin, Yiwei ^{[1
,5
]}

Yao, Jun ^{[8
]}

Shi, Jian ^{[1
,5
]}

Kang, Tiebang ^{[10
]}

Lorkiewicz, Pawel ^{[6
,7
]}

St Clair, Daret ^{[4
,5
]}

Hung, Mien-Chie ^{[9
,11
,12
]}

Evers, B. Mark ^{[1
,3
,5
]}

Zhou, Binhua P. ^{[1
,5
]}

机构：

[1] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40506 USA

[2] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40506 USA

[3] Univ Kentucky, Coll Med, Dept Surg, Lexington, KY 40506 USA

[4] Univ Kentucky, Coll Med, Grad Ctr Toxicol, Lexington, KY 40506 USA

[5] Univ Kentucky, Coll Med, Lucille P Markey Canc Ctr, Lexington, KY 40506 USA

[6] Univ Louisville, Dept Chem, Ctr Regulatory & Environm Analyt Metabol, Louisville, KY 40202 USA

[7] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[10] State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China

[11] China Med Univ, Ctr Mol Med, Taichung, Taiwan

[12] China Med Univ, Grad Inst Canc Biol, Taichung, Taiwan

来源：

CANCER CELL | 2013年 / 23卷 / 03期

基金：

美国国家科学基金会;

关键词：

ISOTOPE-RESOLVED METABOLOMICS; OXIDATIVE STRESS; BETA-CATENIN; LUNG-CANCER; PYRUVATE-KINASE; CELL; PROLIFERATION; TRANSITIONS; GLYCOLYSIS; SURVIVAL;

D O I：

10.1016/j.ccr.2013.01.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The epithelial-mesenchymal transition (EMT) enhances cancer invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We show that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecule biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex 1 activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing the interaction of beta-catenin with T-cell factor. Our study indicates that the loss of FBP1 is a critical oncogenic event in EMT and BLBC.

引用

页码：316 / 331

页数：16

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