ArticleProceedings of the National Academy of Sciences of the United States of America2023
ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Combining bioinformatics and machine learning to analyze and validate sepsis-related cell senescence genes and potential drugs.Renal failure · 2026Article
- Convergent Microenvironment Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Expert reviews in molecular medicine · 2026Review
- The lncRNA DAMER selectively guides mNature cell biology · 2026Article
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- Loss of Atoh8 Impairs Macroautophagy.Cells · 2025Article
- Clinical significance of the S204 phosphorylation of the Smad3 protein in combination with Ki67 for the metastasis and prognosis of gastric cancer.BMC gastroenterology · 2025Observational
- Inducible tag-free degradation of endogenous proteins with AlissAID and development of a photoactivable inducer.Communications biology · 2025Article
- G9a controls plasma cell differentiation through FOXO1 and ETS1 binding site regulatory networks.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- ATOH8 confers the vulnerability of tumor cells to ferroptosis by repressing SCD expression.Cell death and differentiation · 2025Article
- Chemical reprogramming culture for the expansion of salivary gland epithelial basal progenitor cells.Stem cell research & therapy · 2025Article
- Exploring Novel Therapeutic Targets in Breast Cancer via Comprehensive Omics Profiling and Experimental Verification.Biology · 2025Article
- A positive feedback loop between SMAD3 and PINK1 in regulation of mitophagy.Cell discovery · 2025Article
- The emerging role of cellular senescence in amyotrophic lateral sclerosis.Frontiers in neuroscience · 2025Review
- Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform.Cancer gene therapy · 2024Article
- Revolutionizing Senescence Detection: Advancements from Traditional Methods to Cutting-Edge Techniques.Aging and disease · 2024Review
- Review
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor β1 (TGF-β1)-activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53/p16/p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle-promoting genes and consequently causes senescence in lung epithelial cells. Interestingly, the prosenescent SMAD3 converts to being oncogenic and essentially facilitates oncogenic Ras-driven malignant transformation. Furthermore, depleting Atoh8 rapidly accelerates oncogenic Ras-driven lung tumorigenesis, and lung cancers driven by mutant Ras and Atoh8 loss, but not by mutant Ras only, are sensitive to treatment of a specific SMAD3 inhibitor. Moreover, hypermethylation of the
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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.