title: Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133.
abstract: Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.
authors.affiliation: The Catholic University Liver Research Center &WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Hur
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Ryu
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.|BioInformatics Research Center, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Hyun Uk
authors.initials: HU
authors.lastname: Kim
authors.affiliation: The Catholic University Liver Research Center &WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Hong
authors.affiliation: The Catholic University Liver Research Center &WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Eun Byul
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.|BioInformatics Research Center, KAIST, Daejeon 34141, Republic of Korea.|BioProcess Engineering Research Center, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Catholic University Liver Research Center &WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.|Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055442:Metabolome; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013597:Systems Analysis; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; C000606024:Prom1 protein, mouse