ArticleMolecular cancer2019
ASPH-notch Axis guided Exosomal delivery of Prometastatic Secretome renders breast Cancer multi-organ metastasis.
Article in Molecular cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 120 citations in OpenAlex.
- Cell Surface Deazaflavin-Diazirine Energy-Transfer (DarT) Photoproximity Labeling Using Antibody Conjugates.Bioconjugate chemistry · 2026Article
- Hypoxia-induced upregulation of lncRNA SLC9A3-AS1 promotes lung adenocarcinoma progression through the miR-506-5p/ASPH/NOTCH1 pathway.Scientific reports · 2026Article
- Sarcopenia promotes tumorigenesis by disrupting NOTCH-SDC2-regulated biogenesis of muscle-derived extracellular vesicles.Nature communications · 2026Article
- Overexpression and prognostic value of aspartate β-hydroxylase in lung adenocarcinoma: a comprehensive study based on bioinformatics and clinical tissue sample validation.World journal of surgical oncology · 2026Article
- ASPH interacts with RUVBL2 to promote tumor metastasis in lung adenocarcinoma via MAPK and Notch signaling pathways.Frontiers of medicine · 2025Article
- Unveiling tissue heterogeneity through genomic interaction-encoded image representation of RNA-sequencing data.American journal of human genetics · 2025Article
- Article
- Review
- Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multi-omics integration identifies ASPH and PTTG1 as potential causal drivers of lung adenocarcinoma progression and immune evasion.Frontiers in immunology · 2025Article
- Inhibition of Aspartate β-Hydroxylase Enhances Anti-Tumor Immunity.ImmunoTargets and therapy · 2025Article
- Chondrosarcoma: Adjuvant Therapeutic Effects of the ASPH Small Molecule Inhibitor, SMI-1182, With Doxorubicin.Japanese journal of cancer and oncology research · 2025Article
- Ubiquitin-Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Pancreatic cancer cell- and cancer-associated fibroblast-derived exosomes in disease progression, metastasis, and therapy.Discover oncology · 2024Review
- Extracellular vesicle-mediated drug delivery in breast cancer theranostics.Discover oncology · 2024Review
- Identification of prognostic stemness-related genes in kidney renal papillary cell carcinoma.BMC medical genomics · 2024Article
- Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models.International journal of molecular sciences · 2024Article
- The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis.Molecular cancer · 2024Article
- MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.Journal of nanobiotechnology · 2024Article
- Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities.Biological research · 2024Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundAspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This study aims to explore molecular mechanisms underlying how ASPH network regulates designated exosomes to program development and progression of breast cancer.
methodsStable cell lines overexpressing or knocking-out of ASPH were established using lentivirus transfection or CRISPR-CAS9 systems. Western blot, MTT, immunofluorescence, luciferase reporter, co-immunoprecipitation, 2D/3-D invasion, tube formation, mammosphere formation, immunohistochemistry and newly developed in vitro metastasis were applied.
resultsThrough physical interactions with Notch receptors, ligands (JAGs) and regulators (ADAM10/17), ASPH activates Notch cascade to provide raw materials (especially MMPs/ADAMs) for synthesis/release of pro-metastatic exosomes. Exosomes orchestrate EMT, 2-D/3-D invasion, stemness, angiogenesis, and premetastatic niche formation. Small molecule inhibitors (SMIs) of ASPH's β-hydroxylase specifically/efficiently abrogated in vitro metastasis, which mimics basement membrane invasion at primary site, intravasation/extravasation (transendothelial migration), and colonization/outgrowth at distant sites. Multiple organ-metastases in orthotopic and tail vein injection murine models were substantially blocked by a specific SMI. ASPH is silenced in normal adult breast, upregulated from in situ malignancies to highly expressed in invasive/advanced ductal carcinoma. Moderate-high expression of ASPH confers more aggressive molecular subtypes (TNBC or Her2 amplified), early recurrence/progression and devastating outcome (reduced overall/disease-free survival) of breast cancer. Expression profiling of Notch signaling components positively correlates with ASPH expression in breast cancer patients, confirming that ASPH-Notch axis acts functionally in breast tumorigenesis.
conclusionsASPH-Notch axis guides particularly selective exosomes to potentiate multifaceted metastasis. ASPH's pro-oncogenic/pro-metastatic properties are essential for breast cancer development/progression, revealing a potential target for therapy.
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