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Metabolic control of cancer metastasis: role of amino acids at secondary organ sites

Oncogene volume 42, pages 3447–3456 (2023)Cite this article

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Abstract

Most cancer-related deaths are caused by the metastases, which commonly develop at multiple organ sites including the brain, bone, and lungs. Despite longstanding observations that the spread of cancer is not random, our understanding of the mechanisms that underlie metastatic spread to specific organs remains limited. However, metabolism has recently emerged as an important contributor to metastasis. Amino acids are a significant nutrient source to cancer cells and their metabolism which can serve to fuel biosynthetic pathways capable of facilitating cell survival and tumor expansion while also defending against oxidative stress. Compared to the primary tumor, each of the common metastatic sites exhibit vastly different nutrient compositions and environmental stressors, necessitating the need of cancer cells to metabolically thrive in their new environment during colonization and outgrowth. This review seeks to summarize the current literature on amino acid metabolism pathways that support metastasis to common secondary sites, including impacts on immune responses. Understanding the role of amino acids in secondary organ sites may offer opportunities for therapeutic inhibition of cancer metastasis.

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Fig. 1: Amino acid metabolic pathways critical in metastasis and key Inhibitors.
Fig. 2: Amino acid metabolism in the metastatic cascade.
Fig. 3: Amino acid metabolism in secondary niches.

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Acknowledgements

This work was supported by NIH grants R01 CA250506 and R01 CA266767 (to JC), T32 CA009592 (to BK); a VA Merit Award 5101BX000134 and a VA Senior Research Career Scientist Award IK6BX005391 (to JC); and a Department of Defense CDMRP Award W81XWH220109 (to DNE).

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Authors and Affiliations

  1. Program in Cancer Biology, Vanderbilt University, Nashville, TN, 37232, USA

    Breelyn Karno & Jin Chen

  2. Department of Medicine, Division of Rheumatology, Vanderbilt University Medical Center, Nashville, TN, USA

    Deanna N. Edwards & Jin Chen

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

    Deanna N. Edwards & Jin Chen

  4. Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA

    Jin Chen

  5. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA

    Jin Chen

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  1. Breelyn Karno
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  2. Deanna N. Edwards
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  3. Jin Chen
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All the authors determined collectively what topics and ideas should be included in the review. BK wrote the manuscript and DE and JC edited the manuscript.

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Correspondence to Jin Chen.

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Karno, B., Edwards, D.N. & Chen, J. Metabolic control of cancer metastasis: role of amino acids at secondary organ sites. Oncogene 42, 3447–3456 (2023). https://doi.org/10.1038/s41388-023-02868-3

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  • DOI: https://doi.org/10.1038/s41388-023-02868-3

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