ArticleProceedings of the National Academy of Sciences of the United States of America2011
TGF-beta signaling engages an ATM-CHK2-p53-independent RAS-induced senescence and prevents malignant transformation in human mammary epithelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 90 citations in OpenAlex.
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- Ataxia-telangiectasia mutated activation mediates transforming growth factor beta signaling in acetaminophen-induced liver injury in mice.Physiological reports · 2025Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- An adaptive Epithelial-Mesenchymal Transition Program Enables Basal Epithelial Cells to Bypass Stress-Induced Stasis and Contributes to Metaplastic Breast Cancer Progenitor State.Research square · 2024Article
- Regulation of cell function and identity by cellular senescence.The Journal of cell biology · 2024Review
- Multi-omics and single cell characterization of cancer immunosenescence landscape.Scientific data · 2024Article
- RSK3 switches cell fate: from stress-induced senescence to malignant progression.Journal of experimental & clinical cancer research : CR · 2023Article
- Oncogene-Induced Senescence Is a Crucial Antitumor Defense Mechanism of Human Endometrial Stromal Cells.International journal of molecular sciences · 2023Article
- Inflammation and DNA damage: cause, effect or both.Nature reviews. Rheumatology · 2023Review
- Review
- Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular CaInternational journal of molecular sciences · 2022Article
- Preclinical studies for improving radiosensitivity of non-small cell lung cancer cell lines by combining glutaminase inhibition and senolysis.Translational oncology · 2022Article
- Mechanisms and Regulation of Cellular Senescence.International journal of molecular sciences · 2021Review
- FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence.Molecular omics · 2021Article
- Induction and transmission of oncogene-induced senescence.Cellular and molecular life sciences : CMLS · 2021Review
- The Small GTPase RAC1B: A Potent Negative Regulator of-and Useful Tool to Study-TGFβ Signaling.Cancers · 2020Review
- The Histone Code of Senescence.Cells · 2020Review
- Article
- A FAM83A Positive Feed-back Loop Drives Survival and Tumorigenicity of Pancreatic Ductal Adenocarcinomas.Scientific reports · 2019Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogene-induced senescence (OIS), the proliferative arrest engaged in response to persistent oncogene activation, serves as an important tumor-suppressive barrier. We show here that finite lifespan human mammary epithelial cells (HMEC) undergo a p16/RB- and p53-independent OIS in response to oncogenic RAS that requires TGF-β signaling. Suppression of TGF-β signaling by expression of a dominant-negative TGF-β type II receptor, use of a TGF-β type I receptor inhibitor, or ectopic expression of MYC permitted continued proliferation upon RAS expression. Surprisingly, unlike fibroblasts, shRNA-mediated knockdown of ATM or CHK2 was unable to prevent RAS-mediated OIS, arguing that the DNA damage response is not required for OIS in HMEC. Abrogation of TGF-β signaling not only allowed HMEC lacking p53 to tolerate oncogenic RAS but also conferred the capacity for anchorage-independent growth. Thus, the OIS engaged after dysregulated RAS expression provides an early barrier to malignant progression and is mediated by TGF-β receptor activation in HMEC. Understanding the mechanisms that initiate and maintain OIS in epithelial cells may provide a foundation for future therapies aimed at reengaging this proliferative barrier as a 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.