ArticleeLife2022
Machine learning-assisted elucidation of CD81-CD44 interactions in promoting cancer stemness and extracellular vesicle integrity.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- The tetraspanin CD81 regulates the metastasis-promoting function of the osteosarcoma secretome.Biochemistry and biophysics reports · 2026Article
- The Multifaceted Role of Extracellular Vesicles in Triple Negative Breast Cancer.International journal of molecular sciences · 2026Review
- CD81 restricts decidual IGF2-mediated smooth muscle cell dedifferentiation during spiral artery remodeling in preeclampsia.BMC medicine · 2026Article
- Revolutionizing lung cancer screening: the rise of artificial intelligence integrating circulating tumor markers.World journal of surgical oncology · 2026Review
- CD81 promotes proliferation and predicts survival in lung squamous cell carcinoma.Clinical and translational medicine · 2026Article
- Evaluation of Tetraspanins in Extracellular Vesicle Bioengineering.Small science · 2026Article
- Advancing Extracellular Vesicle Research: A Review of Systems Biology and Multiomics Perspectives.Proteomics · 2026Review
- Extracellular Vesicle-Mediated Regulation of H3C14 Contributes to Gemcitabine Resistance in Bladder Cancer.Journal of extracellular vesicles · 2025Article
- Profiling extracellular vesicles from cerebrospinal fluid for classification of intradural spinal tumors.Scientific reports · 2025Article
- Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.medRxiv : the preprint server for health sciences · 2025Article
- Double-positive T cells form heterotypic clusters with circulating tumor cells to foster cancer metastasis.The Journal of clinical investigation · 2025Article
- Helix pomatia agglutinin bound to surface glycans of small extracellular vesicles in-vitro and in-vivo increases in early and late stage breast cancer.Breast cancer (Tokyo, Japan) · 2025Article
- Quantum machine learning-based electrokinetic mining for the identification of nanoparticles and exosomes with minimal training data.Bioactive materials · 2025Article
- Advancing Cancer Biology: Highlights from the 2025 FASEB SRC on Cellular Plasticity in Cancer.Cancer heterogeneity and plasticity · 2025Article
- Role of CD44-Positive Extracellular Vesicles Derived from Highly Metastatic Mouse Mammary Carcinoma Cells in Pre-Metastatic Niche Formation.International journal of molecular sciences · 2024Article
- Microscopic clusters feature the composition of biochemical tetraspanin-assemblies and constitute building-blocks of tetraspanin enriched domains.Scientific reports · 2024Article
- The role and application of vesicles in triple-negative breast cancer: Opportunities and challenges.Molecular therapy oncolytics · 2023Review
- Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer.Cancer discovery · 2023Article
- Deep Learning in Phosphoproteomics: Methods and Application in Cancer Drug Discovery.Proteomes · 2023Review
- Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases.Cancers · 2023Review
Corrections and comments
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Authors and funding
28 authors at 4 institutions in 1 country.
Funding
Abstract
Tumor-initiating cells with reprogramming plasticity or stem-progenitor cell properties (stemness) are thought to be essential for cancer development and metastatic regeneration in many cancers; however, elucidation of the underlying molecular network and pathways remains demanding. Combining machine learning and experimental investigation, here we report CD81, a tetraspanin transmembrane protein known to be enriched in extracellular vesicles (EVs), as a newly identified driver of breast cancer stemness and metastasis. Using protein structure modeling and interface prediction-guided mutagenesis, we demonstrate that membrane CD81 interacts with CD44 through their extracellular regions in promoting tumor cell cluster formation and lung metastasis of triple negative breast cancer (TNBC) in human and mouse models. In-depth global and phosphoproteomic analyses of tumor cells deficient with CD81 or CD44 unveils endocytosis-related pathway alterations, leading to further identification of a quality-keeping role of CD44 and CD81 in EV secretion as well as in EV-associated stemness-promoting function. CD81 is coexpressed along with CD44 in human circulating tumor cells (CTCs) and enriched in clustered CTCs that promote cancer stemness and metastasis, supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights machine learning as a powerful tool in facilitating the molecular understanding of new molecular targets in regulating stemness and metastasis of TNBC.
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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.