title: EMT-induced metabolite signature identifies poor clinical outcome.
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.
authors: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA.|Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX, USA.|Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA.
authors: Salil Kumar
authors: SK
authors: Bhowmik
authors: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Esmeralda
authors: E
authors: Ramirez-Peña
authors: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA.|Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX, USA.|Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA.
authors: James Michael
authors: JM
authors: Arnold
authors: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA.|Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX, USA.|Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA.
authors: Vasanta
authors: V
authors: Putluri
authors: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Nathalie
authors: N
authors: Sphyris
authors: Department of Statistics, University of Michigan, Ann Arbor, MI, USA.
authors: George
authors: G
authors: Michailidis
authors: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA.|Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX, USA.|Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA.
authors: Nagireddy
authors: N
authors: Putluri
authors: Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA.
authors: Stefan
authors: S
authors: Ambs
authors: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA.|Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX, USA.|Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA.
authors: Arun
authors: A
authors: Sreekumar
authors: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Sendurai A
authors: SA
authors: Mani
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods
keywords: EMT; LC-MS metabolomics; breast cancer; metabolic reprogramming; metabolism