1. Cancer Biology
  2. Neuroscience
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Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice

  1. Susu Pan
  2. Kaili Yin
  3. Zhiwei Tang
  4. Shuren Wang
  5. Zhuo Chen
  6. Yirong Wang
  7. Hongxia Zhu
  8. Yunyun Han
  9. Mei Liu  Is a corresponding author
  10. Man Jiang  Is a corresponding author
  11. Ningzhi Xu  Is a corresponding author
  12. Guo Zhang  Is a corresponding author
  1. Huazhong University of Science and Technology, China
  2. Chinese Academy of Medical Sciences and Peking Union Medical College, China
  3. Tongji Medical College, Huazhong University of Science and Technology, China
Research Article
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Cite this article as: eLife 2021;10:e67535 doi: 10.7554/eLife.67535

Abstract

Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological and electrophysiological approaches, we show that hypothalamic oxytocin (Oxt)-producing neurons modulate colitis-associated cancer (CAC) progression in mice. Depletion or activation of Oxt neurons could augment or suppress CAC progression. Importantly, brain treatment with celastrol, a pentacyclic triterpenoid, excites Oxt neurons and inhibits CAC progression, and this anti-tumor effect was significantly attenuated in Oxt neuron-lesioned mice. Furthermore, brain treatment with celastrol suppresses sympathetic neuronal activity in the celiac-superior mesenteric ganglion (CG-SMG), and activation of β2 adrenergic receptor abolishes the anti-tumor effect of Oxt neuron activation or centrally administered celastrol. Taken together, these findings demonstrate that hypothalamic Oxt neurons regulate CAC progression by modulating the neuronal activity in the CG-SMG. Stimulation of Oxt neurons using chemicals, eg. celastrol, might be a novel strategy for colorectal cancer treatment.

Data availability

All data that support the findings of this study are included in this published article and its supplementary files. Source data files have been provided for Figures 1-7.

Article and author information

Author details

  1. Susu Pan

    Department of Toxicology, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Kaili Yin

    Department of Toxicology, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhiwei Tang

    Physiology, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Shuren Wang

    Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Zhuo Chen

    Department of Toxicology, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Yirong Wang

    Physiology, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Hongxia Zhu

    Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yunyun Han

    School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Mei Liu

    Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    For correspondence
    liumei@cicams.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
  10. Man Jiang

    Physiology, Huazhong University of Science and Technology, Wuhan, China
    For correspondence
    manjiang@hust.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0470-8722
  11. Ningzhi Xu

    Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    For correspondence
    xuningzhi@cicams.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
  12. Guo Zhang

    Department of Toxicology, Huazhong University of Science and Technology, Wuhan, China
    For correspondence
    gzhang@hust.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3880-6996

Funding

National Natural Science Foundation of China (81573146)

  • Guo Zhang

National Natural Science Foundation of China (91539125)

  • Guo Zhang

National Natural Science Foundation of China (81972767)

  • Mei Liu

National Natural Science Foundation of China (31871089)

  • Yunyun Han

National Natural Science Foundation of China (31871028)

  • Man Jiang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal procedures were approved by the IACUC at Huazhong University of Science and Technology (#2511).

Reviewing Editor

  1. Ernie Blevins

Publication history

  1. Received: February 14, 2021
  2. Accepted: September 12, 2021
  3. Accepted Manuscript published: September 16, 2021 (version 1)

Copyright

© 2021, Pan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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