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Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling
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- Zhang, Cheng (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Aldrees, Mohammed (author)
- King Saud bin Abdulaziz University for Health Sciences,King Abdullah International Medical Research Center
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- Arif, Muhammad (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- (creator_code:org_t)
- 2019-07-30
- 2019
- English.
- In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 9
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Colorectal cancer is the third most incidental cancer worldwide, and the response rate of current treatment for colorectal cancer is very low. Genome-scale metabolic models (GEMs) are systems biology platforms, and they had been used to assist researchers in understanding the metabolic alterations in different types of cancer. Here, we reconstructed a generic colorectal cancer GEM by merging 374 personalized GEMs from the Human Pathology Atlas and used it as a platform for systematic investigation of the difference between tumor and normal samples. The reconstructed model revealed the metabolic reprogramming in glutathione as well as the arginine and proline metabolism in response to tumor occurrence. In addition, six genes including ODC1, SMS, SRM, RRM2, SMOX, and SAT1 associated with arginine and proline metabolism were found to be key players in this metabolic alteration. We also investigated these genes in independent colorectal cancer patients and cell lines and found that many of these genes showed elevated level in colorectal cancer and exhibited adverse effect in patients. Therefore, these genes could be promising therapeutic targets for treatment of a specific colon cancer patient group.
Subject headings
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Patobiologi (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Pathobiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- genome scale metabolic model
- polyamine metabolism
- personalized medicine
- transcriptomics
- colorectal cancer
Publication and Content Type
- art (subject category)
- ref (subject category)
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- AGRICULTURAL SCIENCES
- AGRICULTURAL SCI ...
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