Loss of FBP1 by snail-mediated repression provides metabolic advantages in basal-like breast cancer

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

doi:10.1016/j.ccr.2013.01.022

Loss of FBP1 by snail-mediated repression provides metabolic advantages in basal-like breast cancer

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

Research output: Contribution to journal › Article › peer-review

587 Scopus citations

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.

Original language	English
Pages (from-to)	316-331
Number of pages	16
Journal	Cancer Cell
Volume	23
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2013.01.022
State	Published - Mar 18 2013

Bibliographical note

Funding Information:
We thank Ms. Ramya Balasubramaniam for technical assistance in metabolomics experiments, Dr. Sam Arumugam at J.G. Brown Cancer Center NMR facility for NMR data acquisition, and Dr. Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (CA125454 to B.P.Z.; CA049797 and CA073599 to D.St.C.; P20CA1530343 to B.M.E.; CA118434-01A2 and 1R01ES022191-01 to T.W.M.F.), Susan G Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), National Science Foundation (EPS-0447479 to T.W.M.F.), Edward P. Evans Foundation (to D.St.C.), and pre-doctoral fellowship (BC101068) from DoD Breast Cancer Research Program (to Y.L.).

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2013.01.022

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@article{3ed26ff270324063bb4c981c12acf6eb,

title = "Loss of FBP1 by snail-mediated repression provides metabolic advantages in basal-like breast cancer",

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.",

author = "Chenfang Dong and Tingting Yuan and Yadi Wu and Yifan Wang and Fan, {Teresa W.M.} and Sumitra Miriyala and Yiwei Lin and Jun Yao and Jian Shi and Tiebang Kang and Pawel Lorkiewicz and {St Clair}, Daret and Hung, {Mien Chie} and Evers, {B. Mark} and Zhou, {Binhua P.}",

note = "Funding Information: We thank Ms. Ramya Balasubramaniam for technical assistance in metabolomics experiments, Dr. Sam Arumugam at J.G. Brown Cancer Center NMR facility for NMR data acquisition, and Dr. Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (CA125454 to B.P.Z.; CA049797 and CA073599 to D.St.C.; P20CA1530343 to B.M.E.; CA118434-01A2 and 1R01ES022191-01 to T.W.M.F.), Susan G Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), National Science Foundation (EPS-0447479 to T.W.M.F.), Edward P. Evans Foundation (to D.St.C.), and pre-doctoral fellowship (BC101068) from DoD Breast Cancer Research Program (to Y.L.). ",

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doi = "10.1016/j.ccr.2013.01.022",

language = "English",

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AU - Dong, Chenfang

AU - Yuan, Tingting

AU - Wu, Yadi

AU - Wang, Yifan

AU - Fan, Teresa W.M.

AU - Miriyala, Sumitra

AU - Lin, Yiwei

AU - Yao, Jun

AU - Shi, Jian

AU - Kang, Tiebang

AU - Lorkiewicz, Pawel

AU - St Clair, Daret

AU - Hung, Mien Chie

AU - Evers, B. Mark

AU - Zhou, Binhua P.

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PY - 2013/3/18

Y1 - 2013/3/18

N2 - 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.

AB - 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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JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Loss of FBP1 by snail-mediated repression provides metabolic advantages in basal-like breast cancer

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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