ArticleFrontiers in molecular biosciences2023
Proteolysis of CD44 at the cell surface controls a downstream protease network.
Article in Frontiers in molecular biosciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations.Nucleic acids research · 2026Article
- LYVE1 ectodomain shedding blunts lymphatic transmigration and clearance of macrophages during kidney injury.JCI insight · 2026Article
- Targeting CD44-Hyaluronic Acid Signalling in Obesity Treatment: Insights from Small Molecules and Nanobioconjugates.Nutrition and metabolic insights · 2026Review
- Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations.bioRxiv : the preprint server for biology · 2025Article
- Digging into the Solubility Factor in Cancer Diagnosis: A Case of Soluble CD44 Protein.Biosensors · 2025Review
- Interferon-mediated NK cell activation increases cytolytic activity against T follicular helper cells and limits antibody response to SARS-CoV-2.Nature immunology · 2025Article
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- Targeted approach to determine the impact of cancer-associated protease variants.Science advances · 2025Article
- Non-Animal Hyaluronic Acid and Probiotics Enhance Skin Health via the Gut-Skin Axis: An In Vitro Study on Bioavailability and Cellular Impact.International journal of molecular sciences · 2025Article
- Tumor necrosis factor-inducible gene 6 protein and its derived peptide ameliorate liver fibrosis by repressing CD44 activation in mice with alcohol-related liver disease.Journal of biomedical science · 2024Article
- CD109 drives pro-tumorigenic cell properties in human non-small cell lung cancer through interaction with desmoglein-2.Research square · 2024Article
- Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection.Sensors (Basel, Switzerland) · 2024Article
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
- The Magic of Proteases: From a Procoagulant and Anticoagulant Factor V to an Equitable Treatment of Its Inherited Deficiency.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell surface receptor cluster of differentiation 44 (CD44) is the main hyaluronan receptor of the human body. At the cell surface, it can be proteolytically processed by different proteases and was shown to interact with different matrix metalloproteinases. Upon proteolytic processing of CD44 and generation of a C-terminal fragment (CTF), an intracellular domain (ICD) is released after intramembranous cleavage by the γ-secretase complex. This intracellular domain then translocates to the nucleus and induces transcriptional activation of target genes. In the past CD44 was identified as a risk gene for different tumor entities and a switch in CD44 isoform expression towards isoform CD44s associates with epithelial to mesenchymal transition (EMT) and cancer cell invasion. Here, we introduce meprin β as a new sheddase of CD44 and use a CRISPR/Cas9 approach to deplete CD44 and its sheddases ADAM10 and MMP14 in HeLa cells. We here identify a regulatory loop at the transcriptional level between ADAM10, CD44, MMP14 and MMP2. We show that this interplay is not only present in our cell model, but also across different human tissues as deduced from GTEx (Gene Tissue Expression) data. Furthermore, we identify a close relation between CD44 and MMP14 that is also reflected in functional assays for cell proliferation, spheroid formation, migration and adhesion.
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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.