Characterization of intracellular metabolic states in the origin of the metabolic reprogramming of cancer cells

Cancer cells have been observed to undergo a metabolic reprogramming in which glycolytic fluxes are upregulated whereas oxidative phosphorylation is downregulated. This metabolic phenotype is known as the Warburg effect and it is observed even under high oxygen conditions. To study the mechanism behind this metabolic reprogramming: - We build a reduced model (RedHuman) from the GEM Recon 2 that is representative of the central carbon metabolism of mammalian cells; - We combine fluxomics and metabolomics data to simulate a normal mammalian cells metabolic phenotype during exponential growth phase and the metabolic phenotype of a cancer cell; - We then analyze the feasible flux ranges of the two simulated metabolic phenotypes.

About this result

This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.

Related concepts

Related publications

Meriç Ataman, Vassily Hatzimanikatis, Joana Raquel Pinto Vieira
2015
Poster talk

Abstract

Official source

https://infoscience.epfl.ch/record/210975?ln=en

About this result

Related concepts (8)

Related concepts

Related publications (6)

Related publications

Understanding reprogramming of cancer cell metabolism using metabolic modeling

Vassily Hatzimanikatis, Maria Masid Barcon, Joana Raquel Pinto Vieira

Cancer cells have been observed to undergo a metabolic reprogramming in which glycolytic fluxes are upregulated whereas oxidative phosphorylation is downregulated. This metabolic phenotype is known as theWarburg effect and it is observed even under high oxygen conditions. To study the mechanism behind this metabolic reprogramming: - We formulate a pipeline for consistently reducing data-driven phenotypic models from a human large genome scale model (GEM). - We reduced a model (PetitHuman) from the GEM Recon 2 [1] that is representative of the central carbon metabolism of mammalian cells. - For this pipeline we combine fluxomics and metabolomics data to simulate a normal mammalian cells metabolic phenotype during exponential growth phase and the metabolic phenotype of a cancer cell. - We then analyze the feasible flux ranges of the two simulated metabolic phenotypes. - Same pipeline is used to reduce consistent data-driven phenotypic networks to study variability across different tumor tissues.

2017

Characterisation of intracellular metabolic states in cells presenting the Warburg phenotype

Vassily Hatzimanikatis, Joana Raquel Pinto Vieira

Cancer cells have been shown to undergo a metabolic reprogramming, known as the Warburg effect, which results in enhanced glycolytic fluxes and down- regulated oxidative phosphorylation even in the presence of abundant oxygen. Experiments show that disruption of expression of enzymes that contribute to the enhancement of this glycolytic flux stimulates oxidative phosphorylation and leads to a decrease in tumor cell proliferation. Such observations have originated much interest in the study of tumor cell metabolism with the purpose of investigating possible targets for the development of new cancer therapies. Nevertheless, to date, the mechanistic details of this metabolic reprogramming, and in particular the physiological conditions that lead to the activation of this metabolic switch, have not been well characterized. Metabolic modeling has proven to be a valuable tool for the investigation of cellular physiology in metabolic engineering studies. Recently Hatzimanikatis and coworkers have developed a new framework called Flux Directionality Profile Analysis (FDPA) that aims to enumerate, characterize and rank all thermodynamically feasible intracellular flux states based on a pre-selected set of metabolic objectives. We apply the proposed methodology on a model of central carbon metabolism of mammalian cells in order to characterize the cellular physiology in terms of intracellular fluxes that are associated with the Warburg phenotype.

2014

Characterization of intracellular metabolic states in cells presenting the Warburg phenotype

Vassily Hatzimanikatis, Joana Raquel Pinto Vieira

- Cancer cells have been shown to undergo a metabolic reprogramming (Warburg effect) characterized by enhanced glycolytic fluxes and down-regulated oxidative phosphorylation even in the presence of abundant oxygen. - Experiments show that disruption of expression of enzymes that contribute to the enhancement of this glycolytic flux stimulates oxidative phosphorylation and leads to a decrease in tumor cell proliferation opening the way to the investigation of new therapeutic targets. - To date, the mechanistic details of this metabolic reprogramming, and in particular the physiological conditions that lead to the activation of this metabolic switch, have not been well characterized. - We apply thermodynamic-based metabolic flux balance analysis (TFBA) on a model of central carbon metabolism of mammalian cells in order to characterize thermodynamically feasible intracellular flux states associated with Warburg phenotype based on a pre-selected set of metabolic objectives.

2014

Metabolism

Metabolism (məˈtæbəlɪzəm, from μεταβολή metabolē, "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy

Metabolomics

Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "sy

Oxidative phosphorylation

Oxidative phosphorylation (UK ɒkˈsɪd.ə.tɪv, US ˈɑːk.sɪˌdeɪ.tɪv ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nut