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 Vol 5: The nutritional phenome of EMT-induced cancer stem-like cells.

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This article is from Oncotarget, volume 5.AbstractThe metabolic features of cancer stem CS cells and the effects of specific nutrients or metabolites on CS cells remain mostly unexplored. A preliminary study to delineate the nutritional phenome of CS cells exploited the landmark observation that upon experimental induction into an epithelial-to-mesenchymal EMT transition, the proportion of CS-like cells drastically increases within a breast cancer cell population. EMT-induced CS-like cells HMLERshEcad and isogenic parental cells HMLERshCntrol were simultaneously screened for their ability to generate energy-rich NADH when cultured in a standardized high-throughput metabolic phenotyping platform comprising 350 wells that were pre-loaded with different carbohydrates-starches, alcohols, fatty acids, ketones, carboxylic acids, amino acids, and bi-amino acids. The generation of -phenetic maps- of the carbon and nitrogen utilization patterns revealed that the acquisition of a CS-like cellular state provided an enhanced ability to utilize additional catabolic fuels, especially under starvation conditions. Crucially, the acquisition of cancer stemness activated a metabolic infrastructure that enabled the vectorial transfer of high-energy nutrients such as glycolysis end products pyruvate, lactate and bona fide ketone bodies β-hydroxybutyrate from the extracellular microenvironment to support mitochondrial energy production in CS-like cells. Metabolic reprogramming may thus constitute an efficient adaptive strategy through which CS-like cells would rapidly obtain an advantage in hostile conditions such as nutrient starvation following the inhibition of tumor angiogenesis. By understanding how specific nutrients could bioenergetically boost EMT-CS-like phenotypes -smart foods- or systemic -metabolic nichotherapies- may be tailored to specific nutritional CSC phenomes, whereas high-resolution heavy isotope-labeled nutrient tracking may be developed to monitor the spatiotemporal distribution and functionality of CS-like cells in real time.

Autor: Cuyas, Elisabet; Corominas-Faja, Bruna; Menendez, Javier A.

Fuente: https://archive.org/

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