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Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden..
NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2015 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 13, no 9, 2014-2026 p.Article in journal (Refereed) Published
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Abstract [en]

Hepatocellular carcinoma (HCC) is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM) for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB) and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1) in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC.

Place, publisher, year, edition, pages
2015. Vol. 13, no 9, 2014-2026 p.
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Cell Biology
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URN: urn:nbn:se:uu:diva-272128DOI: 10.1016/j.celrep.2015.10.045ISI: 000366047000025OAI: oai:DiVA.org:uu-272128DiVA: diva2:893202
Funder
Knut and Alice Wallenberg FoundationNovo NordiskSwedish Research CouncilNovo Nordisk
Available from: 2016-01-12 Created: 2016-01-12 Last updated: 2017-11-30Bibliographically approved

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Asplund, Anna

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