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

2234-943X (ISSN)

Vol. 9 681

Subject Categories

Pathobiology

Medical Genetics

Cancer and Oncology

DOI

10.3389/fonc.2019.00681

More information

Latest update

12/16/2019