ArticleJournal of experimental & clinical cancer research : CR2020
Tubulin Tyrosine Ligase Like 4 (TTLL4) overexpression in breast cancer cells is associated with brain metastasis and alters exosome biogenesis.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Prognostic, diagnostic and therapeutic value of the cancer tubulin code.Cancer metastasis reviews · 2026Review
- Emerging clinical applications of exosomes in breast cancer management from biomarkers to therapeutics.Discover oncology · 2026Review
- Emerging Roles of Tubulin Isoforms and Their Post-Translational Modifications in Microtubule-Based Transport and Cellular Functions.Biomolecules · 2026Review
- OMNIS: a spatially informed multi-omics deep-learning framework for tumor recurrence prediction and primary-metastatic tumor differentiation title page.Frontiers in artificial intelligence · 2026Article
- TTLL4 mediates the PI3K/AKT/MDM2 pathway to promote hepatocellular carcinoma progression and predict patient prognosis.APL bioengineering · 2025Article
- Role of Extracellular Vesicles in the Pathogenesis of Brain Metastasis.Journal of extracellular biology · 2025Review
- Biological profile of breast cancer brain metastasis.Acta neuropathologica communications · 2025Review
- Breaking the premetastatic niche barrier: the role of endothelial cells and therapeutic strategies.Theranostics · 2025Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Extracellular vesicles originating from the mechanical microenvironment in the pathogenesis and applications for cardiovascular diseases.Regenerative therapy · 2024Review
- Tubulin Complexity in Cancer and Metastasis.Advances in experimental medicine and biology · 2024Review
- Extracellular vesicle-mediated pre-metastatic niche formation via altering host microenvironments.Frontiers in immunology · 2024Review
- The role and application of vesicles in triple-negative breast cancer: Opportunities and challenges.Molecular therapy oncolytics · 2023Review
- Exosomes Interactions with the Blood-Brain Barrier: Implications for Cerebral Disorders and Therapeutics.International journal of molecular sciences · 2023Review
- Extracellular vesicles in the treatment and diagnosis of breast cancer: a status update.Frontiers in endocrinology · 2023Review
- Molecular landscape and emerging therapeutic strategies in breast cancer brain metastasis.Therapeutic advances in medical oncology · 2023Review
- Small extracellular vesicles in breast cancer brain metastasis and the prospect of clinical application.Frontiers in bioengineering and biotechnology · 2023Review
- Tumor-Derived Exosomes and Their Role in Breast Cancer Metastasis.International journal of molecular sciences · 2022Review
- Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis.Cancer gene therapy · 2022Article
- Extracellular vesicles and particles impact the systemic landscape of cancer.The EMBO journal · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe survival rate is poor in breast cancer patients with brain metastases. Thus, new concepts for therapeutic approaches are required. During metastasis, the cytoskeleton of cancer cells is highly dynamic and therefore cytoskeleton-associated proteins are interesting targets for tumour therapy.
methodsScreening for genes showing a significant correlation with brain metastasis formation was performed based on microarray data from breast cancer patients with long-term follow up information. Validation of the most interesting target was performed by MTT-, Scratch- and Transwell-assay. In addition, intracellular trafficking was analyzed by live-cell imaging for secretory vesicles, early endosomes and multiple vesicular bodies (MVB) generating extracellular vesicles (EVs). EVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Western blotting, mass spectrometry, and ingenuity pathway analysis (IPA). Effect of EVs on the blood-brain-barrier (BBB) was examined by incubating endothelial cells of the BBB (hCMEC/D3) with EVs, and permeability as well as adhesion of breast cancer cells were analyzed. Clinical data of a breast cancer cohort was evaluated by χ2-tests, Kaplan-Meier-Analysis, and log-rank tests while for experimental data Student's T-test was performed.
resultsAmong those genes exhibiting a significant association with cerebral metastasis development, the only gene coding for a cytoskeleton-associated protein was Tubulin Tyrosine Ligase Like 4 (TTLL4). Overexpression of TTLL4 (TTLL4
conclusionsThese data suggest that TTLL4-mediated microtubule polyglutamylation alters exosome homeostasis by regulating trafficking of MVBs. The TTLL4
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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.