EMT-induced metabolite signature identifies poor clinical outcome

Oncotarget
Salil Kumar BhowmikSendurai A Mani

Abstract

Metabolic reprogramming is a hallmark of cancer. Epithelial-mesenchymal transition (EMT) induces cancer stem cell (CSC) characteristics and promotes tumor invasiveness; however relatively little is known about the metabolic reprogramming in EMT. Here we show that breast epithelial cells undergo metabolic reprogramming following EMT. Relative to control, cell lines expressing EMT transcription factors show ≥1.5-fold accumulation of glutamine, glutamate, beta-alanine and glycylleucine as well as ≥1.5-fold reduction of phosphoenolpyruvate, urate, and deoxycarnitine. Moreover, these metabolic alterations were found to be predictive of overall survival (hazard ratio = 2.3 (95% confidence interval: 1.31-4.2), logrank p-value = 0.03) and define breast cancer molecular subtypes. EMT-associated metabolites are primarily composed of anapleurotic precursors, suggesting that cells undergoing EMT have a shift in energy production. In summary, we describe a unique panel of metabolites associated with EMT and demonstrate that these metabolites have the potential for predicting clinical and biological characteristics associated with patient survival.

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Citations

Jun 21, 2018·Frontiers in Oncology·Vusala SnyderShrikant Anant
Nov 9, 2018·International Journal of Molecular Sciences·Monserrat Olea-FloresNapoleón Navarro-Tito
Apr 3, 2020·International Journal of Molecular Medicine·Chunlei YuanSijia Duan
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Jul 3, 2019·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Zhuocheng YaoFei Zou
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Feb 9, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lotem ZingerIdo Wolf
Sep 3, 2016·Cancer Research·Camille LehuédéPeter M Siegel
Apr 4, 2020·Molecular Metabolism·Aarif Siddiqui, Paolo Ceppi
Dec 11, 2020·British Journal of Cancer·Suhas V VasaikarSendurai A Mani
Oct 1, 2018·Pharmacology & Therapeutics·Mohit Kumar JollyHerbert Levine

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Methods Mentioned

BETA
RNA-seq
PCA
metabolomic profiling
metabolomics profiling

Software Mentioned

LRPath
QQQ Quantitative Analysis B
limma
R
affy
Agilent MassHunter Workstation Data Acquisition
MetScape
SRM
QQQ Qualitative Analysis

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