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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 \u03b22 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, for example, celastrol, might be a novel strategy for colorectal cancer treatment.<\/jats:p>","DOI":"10.7554\/elife.67535","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T06:00:22Z","timestamp":1631772022000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67535","source":"Crossref","is-referenced-by-count":50,"title":["Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice"],"prefix":"10.7554","volume":"10","author":[{"given":"Susu","family":"Pan","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Health, Ministry of Education, Department of Toxicology, School of Public Health, Tongji Medical College","place":["Wuhan, China"]},{"name":"Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology","place":["Wuhan, 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