Volume 34, No 5, May 2024

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 34 Issue 5, May 2024: 345-354   |  Open Access

ORIGINAL ARTICLES

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

Qun Xu¹ , Ying Cao² , Fanni Kong² , Jiaqi Liu¹ , Xin Chen³ , Yifei Zhao³ , Chin-Hui Lai⁴ , Xin Zhou^3,5 , Hao Hu⁴ , Wei Fu^3,5 , Jian Chen⁶ , Jing Yang^1,2,5,7,*

¹State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China
²Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
³Department of General Surgery, Peking University Third Hospital, Beijing, China
⁴Department of Urology, Peking University People’s Hospital, Beijing, China
⁵Peking University Third Hospital Cancer Center, Beijing, China
⁶Chinese Institute for Brain Research, Beijing, China
⁷IDG/McGovern Institute for Brain Research, Peking University, Beijing, China
Correspondence: Jing Yang(jing.yang@pku.edu.cn)

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.

https://doi.org/10.1038/s41422-024-00946-z

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