Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host.

Autor:	Gonzalez-Aponte MF; Department of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA., Damato AR; Department of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA., Simon T; Department of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA., Aripova N; Department of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA., Darby F; Department of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA., Jeon MS; Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center Biostatistics Shared Resource, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Luo J; Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center Biostatistics Shared Resource, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Rubin JB; Department of Pediatrics, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA., Herzog ED; Department of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA. Electronic address: herzog@wustl.edu.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2024 Dec 06. Date of Electronic Publication: 2024 Dec 06.
DOI:	10.1016/j.ccell.2024.11.012
Abstrakt:	Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis despite aggressive therapy. Here, we hypothesized that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We find daily glucocorticoids promote or suppress GBM growth through glucocorticoid receptor (GR) signaling depending on time of day and the clock genes, Bmal1 and Cry. Blocking circadian signals, like vasoactive intestinal peptide or glucocorticoids, dramatically slows GBM growth and disease progression. Analysis of human GBM samples from The Cancer Genome Atlas (TCGA) shows that high GR expression significantly increases hazard of mortality. Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, modulating its growth through clock-controlled cues, like glucocorticoids. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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