2. Academic Validation
  3. Multiple cancer cell types release LIF and Gal3 to hijack neural signals

Multiple cancer cell types release LIF and Gal3 to hijack neural signals

  • Cell Res. 2024 Mar 11. doi: 10.1038/s41422-024-00946-z.
Qun Xu 1,  Ying Cao 2,  Fanni Kong 2,  Jiaqi Liu 1,  Xin Chen 3,  Yifei Zhao 3,  Chin-Hui Lai 4,  Xin Zhou 3 5,  Hao Hu 4,  Wei Fu 3 5,  Jian Chen 6,  Jing Yang 7 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.
  • 2 Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 3 Department of General Surgery, Peking University Third Hospital, Beijing, China.
  • 4 Department of Urology, Peking University People's Hospital, Beijing, China.
  • 5 Peking University Third Hospital Cancer Center, Beijing, China.
  • 6 Chinese Institute for Brain Research, Beijing, China.
  • 7 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China. jing.yang@pku.edu.cn.
  • 8 Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. jing.yang@pku.edu.cn.
  • 9 Peking University Third Hospital Cancer Center, Beijing, China. jing.yang@pku.edu.cn.
  • 10 IDG/McGovern Institute for Brain Research, Peking University, Beijing, China. jing.yang@pku.edu.cn.
PMID: 38467743 DOI: 10.1038/s41422-024-00946-z
Abstract

Neural signals can significantly influence Cancer prognosis. However, how Cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screening then identifies Leukemia Inhibitory Factor (LIF) and Galectin-3 (Gal3) as the key cytokines released by these Cancer cell types to trigger brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that pharmacologic or genetic blockage of Cancer cell-derived LIF or Gal3 signaling abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple Cancer cell types hijacking the nervous system to promote tumor progression.

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