ArticleBreast cancer research : BCR2006
Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial-mesenchymal transition in mammary epithelial cells.
Article in Breast cancer research : BCR, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 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
149 citing papers in PubMed, 236 citations in OpenAlex.
- TGF-β upregulates miR-181a expression to promote breast cancer metastasis.The Journal of clinical investigation · 2013Trial
- Integrin αVβ3 as a context‑dependent regulator of bone homeostasis: Insights into osteoporosis pathogenesis and therapeutic targeting (Review).Molecular medicine reports · 2026Review
- Transforming growth factor-β and integrins: key players in EMT and breast cancer progression.Cancer cell international · 2026Review
- Emerging role of ARHGAP29 in melanoma cell phenotype switching.Molecular oncology · 2026Article
- Integrin β3: structural functions, tumour microenvironment regulatory roles and targeted intervention strategies.Frontiers in immunology · 2026Review
- Tumor Exosomal L1 Cell Adhesion Molecule Promotes Brain Metastasis of Lung Cancer.Research (Washington, D.C.) · 2026Article
- Ly6/uPAR Protein fromMarine drugs · 2025Article
- Exploring the Anticancer, Anti-Inflammatory, and Antibiofilm Efficacy of Endemic Stachys longiflora: Insights into the Phytochemical Composition.ChemistryOpen · 2025Article
- Integrating Genomics and Molecular Biology in Understanding Peritoneal Adhesion.Current issues in molecular biology · 2025Review
- Role of the integrin‑β1/TGF‑β1 signaling pathway in the pathogenesis of pelvic organ prolapse: A study on vaginal wall tissue alterations and molecular dysfunction.Molecular medicine reports · 2025Article
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- A switch from α5β1 to αvβ3 integrin activity contributes to the development of a profibrotic mesenchymal phenotype in trabecular meshwork cells.Frontiers in cell and developmental biology · 2025Article
- Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.NPJ systems biology and applications · 2024Article
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.Genes & diseases · 2024Review
- Oncogenic signaling-mediated regulation of chromatin during tumorigenesis.Cancer metastasis reviews · 2023Review
- Role of integrins in the development of fibrosis in the trabecular meshwork.Frontiers in ophthalmology · 2023Review
- SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells.International journal of molecular sciences · 2022Article
- Review
- CDK7/12/13 inhibition targets an oscillating leukemia stem cell network and synergizes with venetoclax in acute myeloid leukemia.EMBO molecular medicine · 2022Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
introductionTransforming growth factor (TGF)-beta suppresses breast cancer formation by preventing cell cycle progression in mammary epithelial cells (MECs). During the course of mammary tumorigenesis, genetic and epigenetic changes negate the cytostatic actions of TGF-beta, thus enabling TGF-beta to promote the acquisition and development of metastatic phenotypes. The molecular mechanisms underlying this conversion of TGF-beta function remain poorly understood but may involve signaling inputs from integrins.
methodsbeta3 Integrin expression or function in MECs was manipulated by retroviral transduction of active or inactive beta3 integrins, or by transient transfection of small interfering RNA (siRNA) against beta3 integrin. Altered proliferation, invasion, and epithelial-mesenchymal transition (EMT) stimulated by TGF-beta in control and beta3 integrin manipulated MECs was determined. Src involvement in beta3 integrin mediated alterations in TGF-beta signaling was assessed by performing Src protein kinase assays, and by interdicting Src function pharmacologically and genetically.
resultsTGF-beta stimulation induced alphavbeta3 integrin expression in a manner that coincided with EMT in MECs. Introduction of siRNA against beta3 integrin blocked its induction by TGF-beta and prevented TGF-beta stimulation of EMT in MECs. beta3 integrin interacted physically with the TGF-beta receptor (TbetaR) type II, thereby enhancing TGF-beta stimulation of mitogen-activated protein kinases (MAPKs), and of Smad2/3-mediated gene transcription in MECs. Formation of beta3 integrin:TbetaR-II complexes blocked TGF-beta mediated growth arrest and increased TGF-beta mediated invasion and EMT. Dual beta3 integrin:TbetaR-II activation induced tyrosine phosphorylation of TbetaR-II, a phosphotransferase reaction mediated by Src in vitro. Inhibiting Src activity in MECs prevented the ability of beta3 integrin to induce TbetaR-II tyrosine phosphorylation, MAPK activation, and EMT stimulated by TGF-beta. Lastly, wild-type and D119A beta3 integrin expression enhanced and abolished, respectively, TGF-beta stimulation of invasion in human breast cancer cells.
conclusionWe show that beta3 integrin alters TGF-beta signaling in MECs via Src-mediated TbetaR-II tyrosine phosphorylation, which significantly enhanced the ability of TGF-beta to induce EMT and invasion. Our findings suggest that beta3 integrin interdiction strategies may represent an innovative approach to re-establishing TGF-beta mediated tumor suppression in progressing human breast cancers.
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.