Trial reportThe Journal of biological chemistry2012
Identification of function for CD44 intracytoplasmic domain (CD44-ICD): modulation of matrix metalloproteinase 9 (MMP-9) transcription via novel promoter response element.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 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
84 citing papers in PubMed, 125 citations in OpenAlex.
- TGF-β2 promotes autophagy-mediated resistance to doxorubicin in metastatic colon cancer cells via HMGB1.Medical oncology (Northwood, London, England) · 2026Article
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- From matrix to nucleus: CD44 as a central regulator of inflammaging, autophagy, and tissue homeostasis.Biogerontology · 2026Review
- Tumor-enriched circRNA TAFCR1 drives cancer progression and metastasis by disrupting UBE1-dependent TRIM21-mediated CD44 ubiquitination.Biomarker research · 2026Article
- Overcoming resistance in CD44-overexpressing myeloma through combination therapy with ATRA, bortezomib, and NK cells.Cancer immunology, immunotherapy : CII · 2026Article
- Wasteosomes (corpora amylacea) of the human brain accumulate in CD44-positive astrocytes.iScience · 2026Article
- Hyaluronan and Associated Biomarkers: A Longitudinal Cohort Study in Patients with Obesity Following Gastric Bypass Surgery.Obesity surgery · 2026Article
- CD44 facilitates adhesive interactions in airineme-mediated intercellular signaling.bioRxiv : the preprint server for biology · 2025Article
- Osteopontin attenuates the foreign-body response to silicone implants.Nature biomedical engineering · 2025Article
- Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- CD44 facilitates adhesive interactions in airineme-mediated intercellular signaling.Frontiers in cell and developmental biology · 2025Article
- TSG6 promotes epithelial-mesenchymal transition and tumor-associated macrophage polarization through Smad2/3 and MAPK signaling by facilitating TSG6-CD44-TGFβR1 or EGFR complex formation.International journal of biological sciences · 2025Article
- Inhibiting CD44-ICD Attenuates LPS-Induced Initiation of Hepatic Inflammation in Septic Mice.International journal of molecular sciences · 2024Article
- Review
- Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.BMC cancer · 2024Article
- High prevalence of CD44 and its ligand low molecular weight hyaluronan in plasma of HNSCC patients: clinical significance.Molecular biology reports · 2024Article
- Article
- CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.Frontiers in immunology · 2024Review
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
CD44 is a multifunctional cell receptor that conveys a cancer phenotype, regulates macrophage inflammatory gene expression and vascular gene activation in proatherogenic environments, and is also a marker of many cancer stem cells. CD44 undergoes sequential proteolytic cleavages that produce an intracytoplasmic domain called CD44-ICD. However, the role of CD44-ICD in cell function is unknown. We take a major step toward the elucidation of the CD44-ICD function by using a CD44-ICD-specific antibody, a modification of a ChIP assay to detect small molecules, and extensive computational analysis. We show that CD44-ICD translocates into the nucleus, where it then binds to a novel DNA consensus sequence in the promoter region of the MMP-9 gene to regulate its expression. We also show that the expression of many other genes that contain this novel response element in their promoters is up- or down-regulated by CD44-ICD. Furthermore, hypoxia-inducible factor-1α (Hif1α)-responsive genes also have the CD44-ICD consensus sequence and respond to CD44-ICD induction under normoxic conditions and therefore independent of Hif1α expression. Additionally, CD44-ICD early responsive genes encode for critical enzymes in the glycolytic pathway, revealing how CD44 could be a gatekeeper of the Warburg effect (aerobic glycolysis) in cancer cells and possibly cancer stem cells. The link of CD44 to metabolism is novel and opens a new area of research not previously considered, particularly in the study of obesity and cancer. In summary, our results finally give a function to the CD44-ICD and will accelerate the study of the regulation of many CD44-dependent genes.
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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.