Dataset Information

Hepatomasys

ABSTRACT: Metabolic alterations can serve as targets for diagnosis and therapy of cancer. Due to the highly complex regulation of cellular metabolism, definite identification of metabolic pathway alterations remains challenging and requires sophisticated experimentation. Here, we applied a comprehensive kinetic model of the central carbon metabolism (CCM) to characterize metabolic reprogramming in murine liver cancer. We show that relative differences of protein abundances of metabolic enzymes obtained by mass spectrometry can be used to scale maximal enzyme capacities. Model simulations predicted tumor-specific alterations of various components of the CCM, a selected number of which were subsequently verified by in vitro and in vivo experiments. Furthermore, we demonstrate the ability of the kinetic model to identify metabolic pathways whose inhibition results in selective tumor cell killing. Our systems biology approach establishes that combining cellular experimentation with computer simulations of physiology-based metabolic models enables a comprehensive understanding of deregulated energetics in cancer.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

DISEASE(S): Hepatocellular Carcinoma

SUBMITTER: Guido Mastrobuoni

LAB HEAD: Stefan Kempa

PROVIDER: PXD011162 | Pride | 2020-03-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Sample_naming.txt	Txt
	Toni_20130308_GM_Exp80_mouse640_01.raw	Raw
	Toni_20130308_GM_Exp80_mouse640_02.raw	Raw
	Toni_20130308_GM_Exp80_mouse641_01.raw	Raw
	Toni_20130308_GM_Exp80_mouse641_02.raw	Raw

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Publications

Kinetic modelling of quantitative proteome data predicts metabolic reprogramming of liver cancer.

Berndt Nikolaus N Egners Antje A Mastrobuoni Guido G Vvedenskaya Olga O Fragoulis Athanassios A Dugourd Aurélien A Bulik Sascha S Pietzke Matthias M Bielow Chris C van Gassel Rob R Damink Steven W Olde SWO Erdem Merve M Saez-Rodriguez Julio J Holzhütter Hermann-Georg HG Kempa Stefan S Cramer Thorsten T

British journal of cancer 20191210 2

<h4>Background</h4>Metabolic alterations can serve as targets for diagnosis and cancer therapy. Due to the highly complex regulation of cellular metabolism, definite identification of metabolic pathway alterations remains challenging and requires sophisticated experimentation.<h4>Methods</h4>We applied a comprehensive kinetic model of the central carbon metabolism (CCM) to characterise metabolic reprogramming in murine liver cancer.<h4>Results</h4>We show that relative differences of protein abu ...[more]

PMID: 31819186

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