Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling

Cheng Zhang, Mohammed Aldrees, Muhammad Arif, Xiangyu Li, Adil Mardinoglu, Mohammad Azhar Aziz
2019 Frontiers in Oncology  
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
more » ... on 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.
doi:10.3389/fonc.2019.00681 pmid:31417867 pmcid:PMC6682621 fatcat:wntjpuvbbbhelcgrn4cn6to47i