ArticleSignal transduction and targeted therapy2023
Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 17 citations in OpenAlex.
- Extracellular vesicles in breast cancer metastasis: functional insights and advances in single-EV analysis.Cancer metastasis reviews · 2026Review
- RAB4A acts as a negative feedback regulator of extracellular vesicle secretion during TGF-β signaling.The FEBS journal · 2026Article
- Targeting oncogenic TβRI signaling inhibits androgen-independent prostate cancer growth and metastasis.Signal transduction and targeted therapy · 2026Article
- Extracellular Vesicle-Associated IL4 Displays Enhanced Anti-Inflammatory Properties in Microglial Cells.Journal of extracellular biology · 2026Article
- TGF‑β1 in obstructive sleep apnea: linking intermittent hypoxia, upper‑airway remodeling, and systemic comorbidities.Sleep & breathing = Schlaf & Atmung · 2026Review
- Automated Cryo-EM and Supervised Machine Learning Enable Reproducible Characterization of Extracellular Vesicles and Co-Isolating Particles.Journal of extracellular vesicles · 2026Article
- Leveraging Quantitative Proteomics and Extracellular Vesicle Data to Uncover Druggable Receptor Kinases Across Cancers.Journal of extracellular vesicles · 2026Article
- Small extracellular vesicles as system-level regulators and predictive biomarkers in breast cancer progression and chemoresistance.Frontiers in pharmacology · 2026Review
- Cancer-derived extracellular vesicles in natural killer cell immune evasion: Molecular mechanisms and therapeutic insights.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- TGF-β-Enriched Exosomes from Acute Myeloid Leukemia Activate Smad2/3-MMP2 and ERK1/2 Signaling to Promote Leukemic Cell Proliferation, Migration, and Immune Modulation.Current issues in molecular biology · 2025Article
- Review
- Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer.iScience · 2025Article
- Extracellular Vesicles Secreted by Cancer-Associated Fibroblasts Drive Non-Invasive Cancer Cell Progression to Metastasis via TGF-β Signalling Hyperactivation.Journal of extracellular vesicles · 2025Article
- Ginsenoside Rb1 attenuates erythropoietin-exacerbated vascular calcification in chronic kidney disease through BMP2-dependent Smad1/5/9 inhibition.CytoJournal · 2025Article
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- TGF-β regulates the release of breast cancer cell-derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression.Journal of extracellular vesicles · 2024Article
- Article
- Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design.Vaccines · 2024Review
- A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection.Cells · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the leading cause of cancer-related deaths. Transforming growth factor beta (TGF-β) signaling drives metastasis and is strongly enhanced during cancer progression. Yet, the use of on-target TGF-β signaling inhibitors in the treatment of cancer patients remains unsuccessful, highlighting a gap in the understanding of TGF-β biology that limits the establishment of efficient anti-metastatic therapies. Here, we show that TGF-β signaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle (sEV) secretion. Demonstrating sEV's unique role, TGF-β signaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β. Further, genetic disruption of sEV secretion in highly-metastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-β signaling to nearly-normal levels. Otherwise, TGF-β signaling activity in non-invasive breast cancer cells is inherently low, but can be amplified by sEVs, enabling invasion and metastasis of poorly-metastatic breast cancer cells. Underscoring the translational potential of inhibiting sEV trafficking in advanced breast cancers, treatment with dimethyl amiloride (DMA) decreases sEV secretion, TGF-β signaling activity, and breast cancer progression in vivo. Targeting both the sEV trafficking and TGF-β signaling by combining DMA and SB431542 at suboptimal doses potentiated this effect, normalizing the TGF-β signaling in primary tumors to potently reduce circulating tumor cells, metastasis, and tumor self-seeding. Collectively, this study establishes sEVs as critical elements in TGF-β biology, demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-β signaling levels in breast cancer cells.
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.