Gomez, Adrian M, Wu, Yue, Zhang, Chao, Boyd, Leah, Wee, Tse-Luen, Gewolb, Joseph, Amor, Corina, Cheadle, Lucas, Borniger, Jeremy C (December 2025) Aberrant hypothalamic neuronal activity blunts glucocorticoid diurnal rhythms in murine breast cancer. Neuron. S0896-6273(25)00892. ISSN 0896-6273 (Public Dataset)
Abstract
Breast cancer patients often exhibit disrupted diurnal rhythms in circulating glucocorticoids (GCs), such as cortisol. This disruption correlates with reduced quality of life and higher cancer mortality; however, the exact cause of this phenomenon remains unclear. Here, we demonstrate that breast tumor-bearing mice exhibit blunted GC rhythms and a loss of diurnal rhythms in the activity of paraventricular hypothalamic neurons expressing corticotropin-releasing hormone (PVNCRH). This change in neuronal activity is mediated by disinhibition from upstream GABAergic neurons. Using chemogenetics to stimulate PVNCRH neurons at different times of day, we show that stimulation just before the light-to-dark transition restores normal GC rhythms, reduces tumor progression, and increases intra-tumor effector T cells (CD8+). Our findings demonstrate that breast cancer distally regulates neurons in the hypothalamus that control the output of the hypothalamic-pituitary-adrenal (HPA) axis and provide evidence that therapeutic targeting of these neurons could mitigate tumor progression via enhancing anti-tumor immunity.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders organism description > animal diseases & disorders > cancer > cancer types > breast cancer organism description > animal > mammal organism description > animal > mammal > rodent > mouse organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Borniger lab CSHL labs > Spector lab CSHL labs > Cheadle lab CSHL Cancer Center Program CSHL Post Doctoral Fellows |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 15 December 2025 |
| Date Deposited: | 13 Feb 2026 18:37 |
| Last Modified: | 13 Feb 2026 18:37 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/42083 |
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