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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2013 Mar 5

PMID 23453623

Citations 454

Authors

Chenfang Dong

Tingting Yuan

Yadi Wu

Yifan Wang

Teresa W M Fan

Sumitra Miriyala

Yiwei Lin

Jun Yao

Jian Shi

Tiebang Kang

Pawel Lorkiewicz

Daret St Clair

Mien-Chie Hung

B Mark Evers

Binhua P Zhou

Affiliations

Soon will be listed here.

Abstract

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 I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing the interaction of β-catenin with T-cell factor. Our study indicates that the loss of FBP1 is a critical oncogenic event in EMT and BLBC.

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