ArticlePLoS genetics2014
Ras-mediated deregulation of the circadian clock in cancer.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 2 of them syntheses that pooled it.
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Who cites it
100 citing papers in PubMed, 2 syntheses or guidelines pooled it, 155 citations in OpenAlex.
- Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers.Cancer medicine · 2019Pooled it
- Mining for novel candidate clock genes in the circadian regulatory network.BMC systems biology · 2015Pooled it
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- Modulation of the tumor microenvironment through BMAL1-LHX8 axis augments the sensitivity of ameloblastoma to vemurafenib.Journal of advanced research · 2026Article
- The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer.Cancers · 2026Review
- Conserved function of a RasGEF-mediated pathway in the metabolic compensation of the circadian clock.The FEBS journal · 2025Article
- Subtle alteration in transcriptional memory governs the lineage-level cell cycle duration heterogeneities of mammalian cells.iScience · 2025Article
- Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo.PLoS biology · 2025Article
- Article
- Unravelling the link between circadian clock genes and brain tumors: From pathological disruptions to potential therapeutic interventions.Frontiers in pharmacology · 2025Review
- CirRFKB: A knowledgebase of circadian-related risk factors for cancer pathogenesis and personalized medicine.Computational and structural biotechnology journal · 2025Article
- Integrative Computational Framework,bioRxiv : the preprint server for biology · 2024Article
- Novel druggable space in human KRAS G13D discovered using structural bioinformatics and a P-loop targeting monoclonal antibody.Scientific reports · 2024Article
- Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.Aging and disease · 2024Review
- The Relationship between Circadian Rhythm and Cancer Disease.International journal of molecular sciences · 2024Review
- Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.BMC genomics · 2024Article
- MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis.bioRxiv : the preprint server for biology · 2023Article
- MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis.PLoS genetics · 2023Article
- The circadian clock, aging and its implications in cancer.Neoplasia (New York, N.Y.) · 2023Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock.
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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.