ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Disruption of the Clock Component Bmal1 in Mice Promotes Cancer Metastasis through the PAI-1-TGF-β-myoCAF-Dependent Mechanism.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 36 citations in OpenAlex.
- COVID-19 triggers pulmonary tumor outgrowth through hypoxia- and inflammation-induced VEGF-dependent angiogenesis.Signal transduction and targeted therapy · 2026Article
- Article
- Modulation of the tumor microenvironment through BMAL1-LHX8 axis augments the sensitivity of ameloblastoma to vemurafenib.Journal of advanced research · 2026Article
- Deciphering the circadian signature in acute myeloid leukemia: NPAS2 downregulation as a master predictive feature.Blood research · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Circadian Rhythms in Colorectal Cancer: Recent Advances in Development and Treatment.Journal of clinical medicine research · 2026Review
- Role of capsaicin, circadian clock genes, and TRPV1 in colorectal carcinogenesis: Lessons and future directions.Journal of advanced research · 2026Review
- BMAL1 attenuates myocardial infarction-induced fibrosis via suppressing p-SMAD3/SMAD3 in TGF-β1 pathway.Biochemistry and biophysics reports · 2026Article
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- The astrocyte clock controls circadian perineuronal net remodeling, synapse strength and learning behavior.bioRxiv : the preprint server for biology · 2026Article
- The role of circadian disruption, sleep dysregulation, lifestyle factors, and metabolic reprogramming in the pathogenesis and progression of ovarian cancer.Journal of the National Cancer Center · 2026Review
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment.Acta biochimica et biophysica Sinica · 2026Review
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Metastasis in biological time.Frontiers in cell and developmental biology · 2026Review
- Molecular Mechanisms of Symptom Fluctuations in Malignant Tumor Patients: Stable by Day and Severe at Night.Journal of Cancer · 2026Review
- Circadian rhythms in the tumor microenvironment: spatiotemporal immune regulation and chronotherapeutic opportunities.Frontiers in immunology · 2026Review
- Therapeutic Potential of Melatonin in Gastrointestinal Cancers: Molecular Mechanisms, Preclinical Evidence and Clinical Implications.Journal of pineal research · 2026Review
- From neuro-immune command circuits to microbiota-mediated regulation in the gastrointestinal tumor microenvironment.Frontiers in immunology · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
Corrections and comments
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Authors and funding
14 authors at 10 institutions in 3 countries.
Funding
Abstract
The circadian clock in animals and humans plays crucial roles in multiple physiological processes. Disruption of circadian homeostasis causes detrimental effects. Here, it is demonstrated that the disruption of the circadian rhythm by genetic deletion of mouse brain and muscle ARNT-like 1 (Bmal1) gene, coding for the key clock transcription factor, augments an exacerbated fibrotic phenotype in various tumors. Accretion of cancer-associated fibroblasts (CAFs), especially the alpha smooth muscle actin positive myoCAFs, accelerates tumor growth rates and metastatic potentials. Mechanistically, deletion of Bmal1 abrogates expression of its transcriptionally targeted plasminogen activator inhibitor-1 (PAI-1). Consequently, decreased levels of PAI-1 in the tumor microenvironment instigate plasmin activation through upregulation of tissue plasminogen activator and urokinase plasminogen activator. The activated plasmin converts latent TGF-β into its activated form, which potently induces tumor fibrosis and the transition of CAFs into myoCAFs, the latter promoting cancer metastasis. Pharmacological inhibition of the TGF-β signaling largely ablates the metastatic potentials of colorectal cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. Together, these data provide novel mechanistic insights into disruption of the circadian clock in tumor growth and metastasis. It is reasonably speculated that normalization of the circadian rhythm in patients provides a novel paradigm for cancer therapy.
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Registered trials
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.