A polysynaptic hypothalamuspelvic-ganglion circuit regulates prostate tumor growth via WNT3A
- 1Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
Abstract
Brain-tumor communication is increasingly recognized. Peripheral autonomic nerves regulate prostate cancer progression, yet how the brain influences local nerve-tumor interactions remains unclear. We identify a polysynaptic circuit linking the hypothalamic paraventricular nucleus (PVN), dorsal motor nucleus of the vagus (DMV), major pelvic ganglion (MPG) and prostate tumor in mice. Although both nuclei were activated during tumor growth, PVN activity restrained, whereas DMV activity promoted tumor growth. MPG ablation abolished DMV-induced tumor promotion. Combining LMD with Smart-seq2 revealed transcriptional remodeling and increased Wnt3a expression in tumor-innervating, activated MPG neurons under upstream neural control. MPG explants released WNT3A, whose neutralization suppressed explant-induced cancer-cell proliferation. Together, our findings identify a polysynaptic PVN-DMV-MPG circuit that regulates prostate tumor growth and implicate WNT3A as a mediator of the pro-tumor effects of the MPG, highlighting the therapeutic potential of targeting the neural circuit and downstream molecular pathway.
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BibTeX
@misc{ran2026polysynaptic,
title = {{A polysynaptic hypothalamuspelvic-ganglion circuit regulates prostate tumor growth via WNT3A}},
author = {W. Ran and P. Wu and Z. Qiao and S. Wang and Q. Yang and R. Yan and Z. Yan and J. Zhang and B. He and Y. Shao and Y. Wang and S. Chu and Y. Wang and H. Wang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.22.760909},
url = {https://www.biorxiv.org/content/10.64898/2026.10.22.760909v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A polysynaptic hypothalamuspelvic-ganglion circuit regulates prostate tumor growth via WNT3A
AU - W. Ran
AU - P. Wu
AU - Z. Qiao
AU - S. Wang
AU - Q. Yang
AU - R. Yan
AU - Z. Yan
AU - J. Zhang
AU - B. He
AU - Y. Shao
AU - Y. Wang
AU - S. Chu
AU - Y. Wang
AU - H. Wang
PY - 2026
DA - 2026/10/22
PB - bioRxiv
DO - 10.64898/2026.10.22.760909
UR - https://www.biorxiv.org/content/10.64898/2026.10.22.760909v1
AB - Brain-tumor communication is increasingly recognized. Peripheral autonomic nerves regulate prostate cancer progression, yet how the brain influences local nerve-tumor interactions remains unclear. We identify a polysynaptic circuit linking the hypothalamic paraventricular nucleus (PVN), dorsal motor nucleus of the vagus (DMV), major pelvic ganglion (MPG) and prostate tumor in mice. Although both nuclei were activated during tumor growth, PVN activity restrained, whereas DMV activity promoted tumor growth. MPG ablation abolished DMV-induced tumor promotion. Combining LMD with Smart-seq2 revealed transcriptional remodeling and increased Wnt3a expression in tumor-innervating, activated MPG neurons under upstream neural control. MPG explants released WNT3A, whose neutralization suppressed explant-induced cancer-cell proliferation. Together, our findings identify a polysynaptic PVN-DMV-MPG circuit that regulates prostate tumor growth and implicate WNT3A as a mediator of the pro-tumor effects of the MPG, highlighting the therapeutic potential of targeting the neural circuit and downstream molecular pathway.
ER -