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Identifying anti-gr...
Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling
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- Ghaffari Nouran, Pouyan, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Mardinoglu, Adil, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Asplund, Anna (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Science for Life Laboratory, SciLifeLab,Uppsala University
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- Shoaie, Saeed, 1985 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kampf, Caroline (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Science for Life Laboratory, SciLifeLab,Uppsala University
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- Uhlén, Mathias (author)
- KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Nielsen, Jens (author)
- KTH,Science for Life Laboratory, SciLifeLab,Chalmers, Dept Biol & Biol Engn, Sweden,Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2015-02-02
- 2015
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 8183-
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Abstract
Subject headings
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- Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted 85 antimetabolites that can inhibit growth of, or even kill, any of the cell lines, while at the same time not being toxic for 83 different healthy human cell types. 60 of these antimetabolites were found to inhibit growth in all cell lines. Finally, we experimentally validated one of the predicted antimetabolites using two cell lines with different phenotypic origins, and found that it is effective in inhibiting the growth of these cell lines. Using immunohistochemistry, we also showed high or moderate expression levels of proteins targeted by the validated antimetabolite. Identified anti-growth factors for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies.
Subject headings
- NATURVETENSKAP -- Biologi -- Annan biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Other Biological Topics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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