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Jens Nielsen

About Jens Nielsen:
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SEEK ID: https://fairdomhub.org/people/78

Location:  Sweden

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IMOMESIC

IMOMESIC - Integrating Modelling of Metabolism and Signalling towards an Application in Liver Cancer

One of the most challenging questions in cancer research is currently the interconnection of metabolism and signalling. An understanding of mechanisms that facilitate the physiological shift towards a proliferative metabolism in cancer cells is considered a major upcoming topic in oncology and is a key activity for future drug development. Due to the complexity of interrelations, a systems biology
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Public web page: Not specified

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SCaRAB

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Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis
IMOMESIC

Abstract (Expand)

Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to … replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.

Authors: Avlant Nilsson, Jurgen R. Haanstra, Martin Engqvist, Albert Gerding, Barbara M. Bakker, Ursula Klingmüller, Bas Teusink, Jens Nielsen

Date Published: 27th Apr 2020

Publication Type: Journal

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