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Bhowmik SK
; Ramirez-Peņa E
; Arnold JM
; Putluri V
; Sphyris N
; Michailidis G
; Putluri N
; Ambs S
; Sreekumar A
; Mani SA
Oncotarget
2015[Dec]; 6
(40
): 42651-60
PMID26315396
show ga
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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