ArticlePloS one2010
Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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Who cites it
165 citing papers in PubMed, 282 citations in OpenAlex.
- Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2018Trial
- Sympathetic activation links light exposure and rest-activity rhythm to liver injury and bile acid dysregulation.Npj biological timing and sleep · 2026Article
- Dysregulation of circadian clock gene BMAL1 and cell cycle regulator WEE1 in pediatric AML.Molecular biology reports · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Rhythms of risk: the intersection of clocks, cancer, and chronotherapy.The Journal of clinical investigation · 2026Review
- Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026Review
- Circadian clock genes: Their influence on liver metabolism, disease development and treatment (Review).Molecular medicine reports · 2026Review
- Metastasis in biological time.Frontiers in cell and developmental biology · 2026Review
- Neural regulation of tumor progression: implications for hepatocellular carcinoma.Frontiers in immunology · 2026Review
- LILRB4 regulates circadian disruption-induced mammary tumorigenesis via non-canonical WNT signaling pathway.Oncogene · 2025Article
- Chrono-Pharmacology for Cancer: Harnessing Circadian Regulations of the Cell Cycle and Immune Response Dynamics for Precision Therapy.ACS pharmacology & translational science · 2025Review
- Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions.Discover oncology · 2025Article
- The diverse roles of the circadian clock in cancer.Nature cancer · 2025Review
- Rhythm is essential: Unraveling the relation between the circadian clock and cancer.Critical reviews in oncology/hematology · 2025Review
- Frequent Shifts During Chronic Jet Lag Uncouple Liver Rhythms From the Light Cycle in Male Mice.Journal of biological rhythms · 2025Article
- Sympathetic signals beneath the surface: fresh insights from skin and muscle.Frontiers in neuroscience · 2025Review
- Avian circadian clock genes: ontogeny and role for adaptive programming in avian embryos.Frontiers in physiology · 2025Review
- Circadian Deregulation: Back Facing the Sun Toward Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Development.Nutrients · 2024Review
- Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.Hepatoma research · 2024Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Period1 and 2 (Per) or Cryptochrome1 and 2 (Cry) are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone. However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis. METHODOLOGY/PRINCIPAL
findingsMice lacking Per1 and 2, Cry1 and 2, or one copy of Bmal1, all show increased spontaneous and radiation-induced tumor development. The neoplastic growth of Per-mutant somatic cells is not controlled cell-autonomously but is dependent upon extracellular mitogenic signals. Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation. Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. CONCLUSIONS/SIGNIFICANCE: Tumor suppression in vivo is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.