Mapping cancer cell metabolism with 13 C flux analysis: Recent progress and future challenges

Casey Scott Duckwall1, Taylor Athanasaw Murphy1, Jamey Dale Young2
1Department of Chemical and Biomolecular Engineering, PMB 351604, 2301 Vanderbilt Place, Vanderbilt University, Nashville, TN 37235-1604, USA
2Departments of Chemical, Biomolecular Engineering, Molecular Physiology and Biophysics, PMB 351604, 2301 Vanderbilt Place, Vanderbilt University, Nashville, TN 37235 1604, USA
DOI: 10.4103/1477-3163.115422

ABSTRACT

The reprogramming of energy metabolism is emerging as an important molecular hallmark of cancer cells. Recent discoveries linking specific metabolic alterations to cancer development have strengthened the idea that altered metabolism is more than a side effect of malignant transformation, but may in fact be a functional driver of tumor growth and progression in some cancers. As a result, dysregulated metabolic pathways have become attractive targets for cancer therapeutics. This review highlights the application of 13 C metabolic flux analysis (MFA) to map the flow of carbon through intracellular biochemical pathways of cancer cells. We summarize several recent applications of MFA that have identified novel biosynthetic pathways involved in cancer cell proliferation and shed light on the role of specific oncogenes in regulating these pathways. Through such studies, it has become apparent that the metabolic phenotypes of cancer cells are not as homogeneous as once thought, but instead depend strongly on the molecular alterations and environmental factors at play in each case.

Keywords: Aerobic glycolysis, isotopomer analysis, metabolomics, reductive carboxylation, warburg effect