ArticleCommunications biology2022
Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by activating FOXM1 and E2F1.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- The role and potential therapeutic intervention of cellular senescence in intervertebral disc degeneration.Genes & diseases · 2026Review
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Chemical direct conversion of human fibroblasts to mesenchymal stem cells that can alleviate inflammation in vivo.Stem cell research & therapy · 2025Article
- Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs.Genome medicine · 2025Article
- FOXM1: a new therapeutic target of extramammary Paget disease.Scientific reports · 2024Article
- Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence.Frontiers in aging · 2024Article
- FOXM1: A small fox that makes more tracks for cancer progression and metastasis.Seminars in cancer biology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
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Abstract
The multifaceted nature of senescent cell cycle arrest necessitates the targeting of multiple factors arresting or promoting the cell cycle. We report that co-inhibition of ATM and ROCK by KU-60019 and Y-27632, respectively, synergistically increases the proliferation of human diploid fibroblasts undergoing replicative senescence through activation of the transcription factors E2F1 and FOXM1. Time-course transcriptome analysis identified FOXM1 and E2F1 as crucial factors promoting proliferation. Co-inhibition of the kinases ATM and ROCK first promotes the G2/M transition via FOXM1 activation, leading to accumulation of cells undergoing the G1/S transition via E2F1 activation. The combination of both inhibitors increased this effect more significantly than either inhibitor alone, suggesting synergism. Our results demonstrate a FOXM1- and E2F1-mediated molecular pathway enhancing cell cycle progression in cells with proliferative potential under replicative senescence conditions, and treatment with the inhibitors can be tested for senomorphic effect in vivo.
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Registered trials
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