Elucidating tumor-stromal metabolic crosstalk in colorectal cancer through integration of constraint-based models and LC-MS metabolomics.

ABSTRACT: Colorectal cancer (CRC) is a major cause of morbidity and mortality in the United States. Tumor-stromal metabolic crosstalk in the tumor microenvironment promotes CRC development and progression, but exactly how stromal cells, in particular cancer-associated fibroblasts (CAFs), affect the metabolism of tumor cells remains unknown. Here we take a data-driven approach to investigate the metabolic interactions between CRC cells and CAFs, integrating constraint-based modeling and metabolomic profiling. Using metabolomics data, we perform unsteady-state parsimonious flux balance analysis to infer flux distributions for central carbon metabolism in CRC cells treated with or without CAF-conditioned media. We find that CAFs reprogram CRC metabolism through stimulation of glycolysis, the oxidative

SUBMITTER: Wang J 

PROVIDER: S-EPMC8818109 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature