ArticleCell death and differentiation2019
Integrin α6β4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting FEN1 disrupts EIF4A3-mediated MUC1-C autoregulation: a novel strategy to suppress lung adenocarcinoma progression.Cell death & disease · 2026Article
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Integrin β3 Promotes Retinal Neovascularization via Endoplasmic Reticulum Stress-Mediated Endothelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
- DNA methyltransferase Dnmt3ba-mediated epigenetic modulation of Integrin signaling is essential for hematopoietic stem and progenitor cell development.Communications biology · 2025Article
- Caveolae and Rho Kinase: their implication of the senescent cell morphology and the secretion of the SASP in HeLa and A549 cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Brillouin Spectroscopy: A Non-Invasive Method for Assessing the Viscoelastic Properties of Biologically Relevant Polymers.Journal of biomedical materials research. Part A · 2025Article
- Brillouin microscopy analysis of the fibroblast mechanical response to substrate's stiffness.Soft matter · 2025Article
- Mechanotransduction for therapeutic approaches: Cellular aging and rejuvenation.APL bioengineering · 2025Review
- ITGA1, the alpha 1 subunit of integrin receptor, is a novel marker of drug-resistant senescent melanoma cells in vitro.Archives of toxicology · 2025Article
- Mechanical effects in aging of the musculoskeletal system: Molecular signaling and spatial scale alterations.Journal of orthopaedic translation · 2025Review
- Inhibition of the FEN1-PBX1 axis elicits cellular senescence in breast cancer via the increased intracellular reactive oxygen species levels.Journal of translational medicine · 2025Article
- Article
- GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma.Cell death & disease · 2024Article
- Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases.International journal of molecular sciences · 2024Review
- PMEcotoxicology and environmental safety · 2024Article
- FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.JCI insight · 2024Article
- A versatile engineered extracellular vesicle platform simultaneously targeting and eliminating senescent stromal cells and tumor cells to promote tumor regression.Journal of nanobiotechnology · 2024Article
- Cerium oxide nanoparticles-carrying human umbilical cord mesenchymal stem cells counteract oxidative damage and facilitate tendon regeneration.Journal of nanobiotechnology · 2023Article
- Integrin β4 induced epithelial-to-mesenchymal transition involves miR-383 mediated regulation of GATA6 levels.Molecular biology reports · 2023Article
- SIRT1 ubiquitination is regulated by opposing activities of APC/C-Cdh1 and AROS during stress-induced premature senescence.Experimental & molecular medicine · 2023Article
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 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. Here we show that the activation of integrin β4 is essential for IR-induced cellular senescence. IR treatment results in the phosphorylation of integrin β4 at tyrosine residue 1510, leading to activation of the integrin α6β4-Src-AKT signaling pathway. We further reveal that the IR-induced phosphorylation of integrin β4 is regulated by the cholesterol content and membrane fluidity. We also find that IR-induced p53-caspase signaling is independent of integrin α6β4-Src-AKT signaling. Finally, we show that siRNA- or inhibitor-mediated blockade of integrin α6β4-Src-AKT signaling switches the post-irradiation fate from senescence to apoptosis, under p53 activated condition, in both cancer cells and tumor tissues of xenograft mice. On the basis of our finding that, integrin α6β4 is specifically activated and acts primarily to induce premature senescence in irradiated cancer cells, we propose that this integrin may be a valuable target and biomarker for radiotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.