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Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization

Björnson, Elias, 1988 (author)
Chalmers tekniska högskola,Chalmers University of Technology,Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.
Mukhopadhyay, B. (author)
National Institute on Alcohol Abuse and Alcoholism,NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
Asplund, Anna (author)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Pristovsek, N. (author)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Cinar, R. (author)
National Institute on Alcohol Abuse and Alcoholism,NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
Romeo, Stefano, 1976 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Center for Cardiovascular and Metabolic Research (CMR),Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg,Univ Gothenburg, Wallenberg Lab, Sahlgrenska Ctr Cardiovasc & Metab Res, Dept Mol & Clin Med, S-41345 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, S-41650 Gothenburg, Sweden.;Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Clin Nutr Unit, I-88100 Catanzaro, Italy.
Uhlén, Mathias (author)
KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Dept Prote, S-10691 Stockholm, Sweden.;KTH Royal Inst Technol, Sci Life Lab, S-17121 Stockholm, Sweden.
Kunos, G. (author)
National Institute on Alcohol Abuse and Alcoholism,NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
Nielsen, Jens B, 1962 (author)
Chalmers tekniska högskola,Chalmers University of Technology,Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.;KTH Royal Inst Technol, Sci Life Lab, S-17121 Stockholm, Sweden.
Mardinoglu, Adil, 1982 (author)
Chalmers tekniska högskola,Chalmers University of Technology,Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.;KTH Royal Inst Technol, Sci Life Lab, S-17121 Stockholm, Sweden.
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Chalmers tekniska högskola Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden (creator_code:org_t)
Elsevier BV, 2015
2015
English.
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 13:9, s. 2014-2026
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

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