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Colorectal Cancer and Metabolism

Current Colorectal Cancer Reports

Abstract

Purpose of Review

Metabolic reprogramming is essential for the rapid proliferation of cancer cells and is thus recognized as a hallmark of cancer. In this review, we will discuss the etiologies and effects of metabolic reprogramming in colorectal cancer.

Recent Findings

Changes in cellular metabolism may precede the acquisition of driver mutations ultimately leading to colonocyte transformation. Oncogenic mutations and loss of tumor suppressor genes further reprogram CRC cells to upregulate glycolysis, glutaminolysis, one-carbon metabolism, and fatty acid synthesis. These metabolic changes are not uniform throughout tumors, as subpopulations of tumor cells may rely on different pathways to adapt to nutrient availability in the local tumor microenvironment. Finally, metabolic cross-communication between stromal cells, immune cells, and the gut microbiota enable CRC growth, invasion, and metastasis.

Summary

Altered cellular metabolism occurs in CRC at multiple levels, including in the cells that make up the bulk of CRC tumors, cancer stem cells, the tumor microenvironment, and host-microbiome interactions. This knowledge may inform the development of improved screening and therapeutics for CRC.

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Acknowledgements

This work was supported by National Institutes of Health grants R01DK099204 to C.S.W., 1F30DK120149 and T32GM007347 to R.E.B., 5F32 DK108492 to S.P.S., P30DK058404 (Vanderbilt Digestive Disease Research Center); and an Office of Medical Research, Department of Veterans Affairs (Merit Review Grants) 1I01 BX001426 to C.S.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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  1. Program in Cancer Biology, Vanderbilt University, Nashville, TN, USA

    Rachel E. Brown, Sarah P. Short & Christopher S. Williams

  2. Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN, USA

    Rachel E. Brown & Christopher S. Williams

  3. Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, B2215 Garland Ave., 1065D MRB-IV, Nashville, TN, 37232-0252, USA

    Sarah P. Short & Christopher S. Williams

  4. Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Christopher S. Williams

  5. Veterans Affairs Tennessee Valley HealthCare System, Nashville, TN, USA

    Christopher S. Williams

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Brown, R.E., Short, S.P. & Williams, C.S. Colorectal Cancer and Metabolism. Curr Colorectal Cancer Rep 14, 226–241 (2018). https://doi.org/10.1007/s11888-018-0420-y

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