ArticlePloS one2019
ERK-mediated TIMELESS expression suppresses G2/M arrest in colon cancer cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- TIMELESS promotes glioma stemness and malignancy through JAK-STAT3 pathway.The Journal of biological chemistry · 2026Article
- Circadian Clock Genes in Colorectal Cancer: From Molecular Mechanisms to Chronotherapeutic Applications.Biomedicines · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- TCM-Driven Circadian Modulation in Cancer: Engineering Spatiotemporal Drug Delivery for Precision Oncology.International journal of nanomedicine · 2026Review
- Circadian disruption associated with nighttime light exposure contributes to airway epithelial remodeling viaFrontiers in pediatrics · 2026Article
- TIMELESS as a prognostic biomarker and therapeutic target in gastric cancer.Journal, genetic engineering & biotechnology · 2025Article
- Article
- c-Jun N-terminal kinase signaling in aging.Frontiers in aging neuroscience · 2024Review
- Podoplanin promotes cell proliferation, survival, and migration of canine non-tonsillar squamous cell carcinoma.The Journal of veterinary medical science · 2023Article
- The role of circadian clocks in cancer: Mechanisms and clinical implications.Genes & diseases · 2023Review
- The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023Review
- Circadian clock as a possible control point in colorectal cancer progression (Review).International journal of oncology · 2022Review
- Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism.Cell death and differentiation · 2022Article
- Circadian Rhythm Dysregulation and Leukemia Development: The Role of Clock Genes as Promising Biomarkers.International journal of molecular sciences · 2022Review
- UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis.Molecular medicine (Cambridge, Mass.) · 2022Article
- Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9.Journal of experimental & clinical cancer research : CR · 2021Article
- KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition.eLife · 2021Article
- Circadian clock genes promote glioma progression by affecting tumour immune infiltration and tumour cell proliferation.Cell proliferation · 2021Article
- Aminoacylase 1 (ACY-1) Mediates the Proliferation and Migration of Neuroblastoma Cells in Humans Through the ERK/Transforming Growth Factor β (TGF-β) Signaling Pathways.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- New Insights Into Cancer Chronotherapies.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The cell cycle is under circadian regulation. Oncogenes can dysregulate circadian-regulated genes to disrupt the cell cycle, promoting tumor cell proliferation. As a regulator of G2/M arrest in response to DNA damage, the circadian gene Timeless Circadian Clock (TIMELESS) coordinates this connection and is a potential locus for oncogenic manipulation. TIMELESS expression was evaluated using RNASeq data from TCGA and by RT-qPCR and western blot analysis in a panel of colon cancer cell lines. TIMELESS expression following ERK inhibition was examined via western blot. Cell metabolic capacity, propidium iodide, and CFSE staining were used to evaluate the effect of TIMELESS depletion on colon cancer cell survival and proliferation. Cell metabolic capacity following TIMELESS depletion in combination with Wee1 or CHK1 inhibition was assessed. TIMELESS is overexpressed in cancer and required for increased cancer cell proliferation. ERK activation promotes TIMELESS expression. TIMELESS depletion increases γH2AX, a marker of DNA damage, and triggers G2/M arrest via increased CHK1 and CDK1 phosphorylation. TIMELESS depletion in combination with Wee1 or CHK1 inhibition causes an additive decrease in cancer cell metabolic capacity with limited effects in non-transformed human colon epithelial cells. The data show that ERK activation contributes to the overexpression of TIMELESS in cancer. Depletion of TIMELESS increases γH2AX and causes G2/M arrest, limiting cell proliferation. These results demonstrate a role for TIMELESS in cancer and encourage further examination of the link between circadian rhythm dysregulation and cancer cell proliferation.
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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.