Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization

被引：143

作者：

Bjornson, Elias ^{[1
]}

Mukhopadhyay, Bani ^{[2
]}

Asplund, Anna ^{[3
]}

Pristovsek, Nusa ^{[3
]}

Cinar, Resat ^{[2
]}

Romeo, Stefano ^{[4
,5
,6
]}

Uhlen, Mathias ^{[7
,8
]}

Kunos, George ^{[2
]}

Nielsen, Jens ^{[1
,8
]}

Mardinoglu, Adil ^{[1
,8
]}

机构：

[1] Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden

[2] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA

[3] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75185 Uppsala, Sweden

[4] Univ Gothenburg, Wallenberg Lab, Sahlgrenska Ctr Cardiovasc & Metab Res, Dept Mol & Clin Med, S-41345 Gothenburg, Sweden

[5] Sahlgrens Univ Hosp, Dept Cardiol, S-41650 Gothenburg, Sweden

[6] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Clin Nutr Unit, I-88100 Catanzaro, Italy

[7] KTH Royal Inst Technol, Dept Prote, S-10691 Stockholm, Sweden

[8] KTH Royal Inst Technol, Sci Life Lab, S-17121 Stockholm, Sweden

来源：

CELL REPORTS | 2015年 / 13卷 / 09期

基金：

瑞典研究理事会;

关键词：

FATTY-ACID OXIDATION; GENOME-SCALE MODELS; METABOLIC NETWORK; GLUTAMINE-METABOLISM; TUMOR-CELLS; CANCER; EXPRESSION; TRANSCRIPTOMICS; IDENTIFICATION; PROTEOME;

D O I：

10.1016/j.celrep.2015.10.045

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：2014 / 2026

页数：13

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