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Neurotransmitter signaling: a new frontier in colorectal cancer biology and treatment

Oncogene volume 41, pages 4769–4778 (2022)Cite this article

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Abstract

The brain–gut axis, a bidirectional network between the central and enteric nervous system, plays a critical role in modulating the gastrointestinal tract function and homeostasis. Recently, increasing evidence suggests that neuronal signaling molecules can promote gastrointestinal cancers, however, the mechanisms remain unclear. Aberrant expression of neurotransmitter signaling genes in colorectal cancer supports the role of neurotransmitters to stimulate tumor growth and metastatic spread by promoting cell proliferation, migration, invasion, and angiogenesis. In addition, neurotransmitters can interact with immune and endothelial cells in the tumor microenvironment to promote inflammation and tumor progression. As such, pharmacological targeting of neurotransmitter signaling represent a promising novel anticancer approach. Here, we present an overview of the current evidence supporting the role of neurotransmitters in colorectal cancer biology and treatment.

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Fig. 1: Interaction between neurotransmitters, colorectal cancer, and tumor microenvironment.

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Acknowledgements

We thank David W. Craig for critical reading of the paper.

Funding

This work was partly supported by National Cancer Institute (grant numbers P30CA014089 and R01CA241137), Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Gene Gregg Pancreas Research Fund, San Pedro Peninsula Cancer Guild, Daniel Butler Research Fund, V foundation for cancer research, Victoria and Philip Wilson Research Fund, Fong research project, Ming Hsieh research fund, Boyd and Elsie Welin Professorship to JCS and USC Trustee Tsai family fund to JCS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute of the National Institutes of Health.

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Authors and Affiliations

  1. Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Francesca Battaglin, Priya Jayachandran, Annika Lenz, Sandra Algaze, Shivani Soni, Jae Ho Lo, Wu Zhang, Evanthia T. Roussos Torres, Shannon M. Mumenthaler & Heinz-Josef Lenz

  2. Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, CA, USA

    Carly Strelez & Shannon M. Mumenthaler

  3. Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Yan Yang & Joshua Millstein

  4. Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA

    Jean C. Shih

  5. Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA

    Shannon M. Mumenthaler

  6. Department of Neurological Surgery, USC Brain Tumor Center, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Josh Neman

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  1. Francesca Battaglin
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Contributions

FB drafted the paper with the aid of CS and AL. HJL supervised the paper. All authors directly provided their contribution, read and approved the final paper.

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Correspondence to Heinz-Josef Lenz.

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Battaglin, F., Jayachandran, P., Strelez, C. et al. Neurotransmitter signaling: a new frontier in colorectal cancer biology and treatment. Oncogene 41, 4769–4778 (2022). https://doi.org/10.1038/s41388-022-02479-4

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  • DOI: https://doi.org/10.1038/s41388-022-02479-4

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