Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling
Journal article, 2019
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.
genome scale metabolic model
polyamine metabolism
personalized medicine
transcriptomics
colorectal cancer
Author
Cheng Zhang
Royal Institute of Technology (KTH)
Mohammed Aldrees
King Saud bin Abdulaziz University for Health Sciences
King Abdullah International Medical Research Center
Ministry of the National Guard - Health Affairs
Muhammad Arif
Royal Institute of Technology (KTH)
Xiangyu Li
Royal Institute of Technology (KTH)
Adil Mardinoglu
King's College London
Royal Institute of Technology (KTH)
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Mohammad Azhar Aziz
King Abdullah International Medical Research Center
Ministry of the National Guard - Health Affairs
King Saud bin Abdulaziz University for Health Sciences
Frontiers in Oncology
2234943x (eISSN)
Vol. 9 681Subject Categories
Pathobiology
Medical Genetics
Cancer and Oncology
DOI
10.3389/fonc.2019.00681