Affinage

CD44

CD44 antigen · UniProt P16070

Length
742 aa
Mass
81.5 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD44 is a transmembrane glycoprotein that serves as the principal cell-surface receptor for hyaluronan (HA), mediating HA endocytosis and routing it to lysosomes for degradation, although the protein itself has no intrinsic catalytic activity toward HA (PMID:1370836). HA recognition is conformationally gated by glycosylation: N-linked glycans at multiple sites within the HA-recognition domain, together with membrane-proximal glycosaminoglycan attachment motifs, are required for binding, and the avidity of the interaction scales with HA size, receptor density, and an inducible activation state that controls ligand retention (PMID:8601595, PMID:10871609). CD44 transduces these adhesive cues into intracellular signaling and is regulated by sequential proteolysis: ADAM10-catalyzed ectodomain shedding, augmented by CD44 ligation and Rac1-driven cytoskeletal remodeling, is followed by γ-secretase intramembrane cleavage to liberate a CD44 intracellular domain (CD44-ICD) that enters the nucleus and activates transcription (PMID:14623895, PMID:15596040). Through its cytoplasmic tail CD44 couples to cytoskeletal and signaling machinery—binding IQGAP1, signaling via RhoA to sustain YAP/Hippo output, and engaging Syk/Rac1/PI3K to act as a phagocytic receptor independent of Fc receptors (PMID:16455948, PMID:21117172, PMID:25101858). CD44 functions as a Wnt co-receptor by associating with and positioning LRP6 (PMID:25301071), suppresses TLR2-driven NF-κB inflammation via its cytoplasmic domain (PMID:18322236), and promotes lymphocyte survival by engaging PI3K-Akt to limit Fas-mediated apoptosis (PMID:20079666, PMID:7545465). In cancer, CD44 supports Kras-MAPK-driven lung adenocarcinoma, drives invasion through a Snail1→MT1-MMP axis, sustains stemness and proliferation through CD44-ICD-dependent transcription, and orchestrates endocytosis of iron-bound hyaluronates that catalyzes histone demethylation to enforce mesenchymal epigenetic plasticity through an iron-CD44 positive feedback loop (PMID:25566991, PMID:32747755, PMID:23208496, PMID:35954411). CD44 itself is transcriptionally repressed by the androgen receptor through a defined androgen-response-element silencer (PMID:33687952).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1992 High

    Established CD44's core physiological function—whether the HA receptor merely binds HA or actively clears it—by showing it drives HA internalization and lysosomal degradation without itself being catalytic.

    Evidence Radiolabeled and fluorescent HA uptake/degradation assays with antibody blocking and lysosomal inhibitors in fibroblasts and macrophages

    PMID:1370836

    Open questions at the time
    • Did not define the molecular determinants of HA binding affinity
    • Mechanism coupling surface binding to internalization not resolved
  2. 1996 High

    Resolved why HA-binding capacity varies between cell types by demonstrating that N-linked glycosylation and GAG-attachment motifs maintain the HA-recognition domain in a binding-competent conformation.

    Evidence Tunicamycin treatment plus systematic site-directed mutagenesis of glycosylation sites with HA-adhesion readout in transfectants

    PMID:8601595

    Open questions at the time
    • Structural basis of the conformational requirement not directly determined
    • Cell-type-specific glycosylation enzymes not identified
  3. 2000 High

    Quantified how CD44 retains HA by showing multivalent, size-dependent binding and an inducible activation state that slows ligand dissociation, distinguishing avidity control from affinity.

    Evidence Competitive binding with defined HA oligomers and kinetic dissociation studies, plus activating mAb

    PMID:10871609

    Open questions at the time
    • Molecular nature of the activation state not defined
    • In vivo relevance of multivalency not established
  4. 2003 High

    Identified the protease and cytoskeletal trigger for CD44 ectodomain release, linking receptor ligation to ADAM10-dependent shedding and tumor cell migration.

    Evidence ADAM10 RNAi, metalloproteinase inhibitors, and FRET imaging of Rac1 activation with migration assays

    PMID:14623895

    Open questions at the time
    • Did not address downstream fate of the shed ectodomain or the membrane-retained stub
  5. 2004 Medium

    Placed shedding in a regulated intramembrane proteolysis sequence, establishing that γ-secretase releases a transcriptionally active CD44-ICD after ectodomain cleavage.

    Evidence Biochemical cleavage analysis, γ-secretase inhibition, and nuclear translocation assays (review-level synthesis)

    PMID:15596040

    Open questions at the time
    • Direct transcriptional targets of CD44-ICD not enumerated here
    • Review-level detail; primary mechanistic data limited
  6. 2006 High

    Demonstrated CD44 acts as a bona fide phagocytic receptor, defining a Syk/Rac1/PI3K signaling route distinct from Fc-receptor phagocytosis.

    Evidence HA-bead and anti-CD44-opsonized erythrocyte engulfment in CD44-knockout macrophages with Syk/PI3K inhibitors

    PMID:16455948

    Open questions at the time
    • Direct biochemical link between CD44 tail and Syk recruitment not shown
    • Physiological clearance targets in vivo not defined
  7. 2008 Medium

    Revealed an immunoregulatory function by showing CD44 physically associates with TLR2 and dampens NF-κB-driven inflammation through its cytoplasmic domain.

    Evidence Co-IP of CD44/TLR2, cytoplasmic-domain deletion constructs, and in vivo cytokine measurement

    PMID:18322236

    Open questions at the time
    • Single-lab study without reciprocal validation across systems
    • Cytoplasmic effector mediating NF-κB suppression unidentified
  8. 2010 High

    Defined a subset-specific survival role, showing CD44 engages PI3K-Akt to limit Fas-mediated apoptosis and enable Th1 memory generation.

    Evidence CD44-deficient mice with Th1/Th2/Th17/CD8 subset comparison and apoptosis/PI3K-Akt readouts

    PMID:20079666

    Open questions at the time
    • Why the survival function is Th1-restricted despite equal expression unexplained
  9. 2010 Medium

    Connected CD44's cytoplasmic tail to the actin cytoskeleton by identifying an endogenous CD44-IQGAP1 complex.

    Evidence Phospho/non-phospho C-terminal peptide pull-down with MS identification and Co-IP of endogenous complex

    PMID:21117172

    Open questions at the time
    • Functional consequence of the interaction not tested
    • Phosphorylation dependence not resolved functionally
  10. 2014 High

    Established CD44 as a Wnt pathway co-receptor acting at the level of LRP6 to tune β-catenin signaling.

    Evidence Reciprocal Co-IP, knockdown/overexpression reporter assays, epistasis, and Xenopus morphant validation

    PMID:25301071

    Open questions at the time
    • Mechanism by which CD44 controls LRP6 membrane localization not defined
  11. 2014 Medium

    Linked CD44 to Hippo output by showing it signals through RhoA to maintain YAP expression and nuclear localization.

    Evidence CD44 RNAi with constitutively active RhoA rescue and YAP-target qRT-PCR plus phenotypic assays

    PMID:25101858

    Open questions at the time
    • How CD44 activates RhoA not established
    • Single-lab study
  12. 2012 Medium

    Provided in vivo genetic evidence that CD44 is required for Kras-MAPK signaling and lung adenocarcinoma formation.

    Evidence CD44 deletion in a KrasG12D lung cancer mouse model with MAPK, tumor burden, and survival analysis

    PMID:23208496

    Open questions at the time
    • Biochemical step linking CD44 to MAPK activation undefined
    • Single-lab study
  13. 2015 Medium

    Defined a pro-invasive signaling axis, placing CD44 upstream of Snail1-driven MT1-MMP expression in pancreatic cancer.

    Evidence CD44 knockdown/overexpression with Snail1/MT1-MMP western blots, invasion assays, and in vivo tumor models

    PMID:25566991

    Open questions at the time
    • Mechanism by which CD44 induces Snail1 not defined
    • Single-lab study
  14. 1995 Medium

    Positioned CD44 as a selective anti-apoptotic signal that counteracts TCR- and glucocorticoid-induced but not p53-dependent death.

    Evidence Anti-CD44/HA ligation with DNA fragmentation and Bcl-2 analysis in a T-cell line

    PMID:7545465

    Open questions at the time
    • Downstream survival effector not identified (Bcl-2 excluded)
    • Single cell-line system
  15. 2018 Medium

    Identified CD44 as the required receptor for GPNMB-mediated anti-inflammatory neuroprotection in astrocytes.

    Evidence Recombinant GPNMB on CD44-knockout primary astrocytes with iNOS/NO/ROS/IL-6 readouts

    PMID:29519253

    Open questions at the time
    • Direct CD44-GPNMB binding not demonstrated
    • Downstream signaling not mapped
  16. 2020 High

    Uncovered a non-canonical role linking CD44 endocytosis to the epigenome, showing iron-bound HA uptake catalyzes histone demethylation and drives mesenchymal plasticity through an iron-CD44 feedback loop.

    Evidence Iron-HA endocytosis assays, histone methylation profiling, iron-homeostasis perturbation, and EMT assays in cancer cells and tumors

    PMID:32747755

    Open questions at the time
    • Specific demethylases catalyzing the marks not identified
    • Mechanism of nuclear iron delivery from endosome unresolved
  17. 2021 Medium

    Tied CD44-ICD transcriptional output to glioblastoma stemness and senescence escape, and linked CD44 to a HAS2/hyaluronan feedback circuit.

    Evidence CRISPR CD44 knockout with RNA-seq, DAPT γ-secretase inhibition, and proliferation/stemness/senescence assays

    PMID:35954411

    Open questions at the time
    • Direct CD44-ICD target genes not defined
    • Single-lab study
  18. 2021 Medium

    Defined a role for CD44 in transformed-cell survival by controlling COL17A1 membrane accumulation and suppressing mitochondrial-ROS-driven ferroptosis during cell extrusion.

    Evidence Plasma-membrane proteomics, COL17A1 knockout in RasV12 cells, metabolomics, and ROS/ferroptosis assays

    PMID:34087104

    Open questions at the time
    • Mechanism by which CD44 stabilizes COL17A1 at the membrane not defined
    • Single-lab study
  19. 2021 High

    Established upstream transcriptional control of CD44, identifying an androgen-receptor silencer element that directly represses CD44 expression.

    Evidence AR ChIP-seq, transcriptomics, CRISPR mutagenesis of the androgen response element, and tumor expression correlation

    PMID:33687952

    Open questions at the time
    • Functional consequence of AR-driven CD44 loss in vivo not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD44's diverse, context-specific signaling outputs (Wnt, Hippo, MAPK, TLR, phagocytosis, epigenetic plasticity) are selected by a single short cytoplasmic tail in a given cell type remains unresolved.
  • No unifying model linking ligand/glycosylation state to downstream pathway choice
  • Structural basis of CD44-ICD transcriptional activity uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005764 lysosome 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-4839726 Chromatin organization 1
Partners
ADAM10COL17A1GPNMBIQGAP1LRP6TLR2

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CD44 mediates the endocytosis and lysosomal degradation of hyaluronan; antibodies against CD44 block HA uptake and internalization in fibroblasts and macrophages, and agents blocking lysosomal acidification (chloroquine, NH4Cl) inhibit subsequent HA degradation. CD44 itself lacks intrinsic degradative activity, as isolated membrane preparations containing CD44 do not break down HA. Isotopic labeling of hyaluronan, molecular-sieve chromatography, antibody blocking, fluorescein-tagged HA internalization assay, lysosomal inhibitors The Journal of cell biology High 1370836
1996 N-linked glycosylation of CD44 is required for hyaluronan binding; tunicamycin abolishes HA-mediated cell adhesion, while mutation of any one of five N-linked glycosylation sites within the HA-recognition domain abrogates binding. Mutation of Ser-Gly motifs providing glycosaminoglycan attachment sites in the membrane-proximal domain also impairs HA binding, indicating that specific glycosylation patterns maintain the HA-recognition domain in the appropriate conformation. Tunicamycin treatment, deoxymannojirimycin treatment, site-directed mutagenesis of N-linked glycosylation sites, stable transfection of CD44 mutants, cell adhesion assay on HA-coated substrate The Journal of cell biology High 8601595
2000 HA binding at the cell surface involves multivalent interactions dependent on HA size, CD44 density, and CD44 activation state. Monovalent binding requires 6–18 sugar residues; divalent binding begins at ~20–38 residues. An inducing anti-CD44 mAb (IRAWB14) dramatically slows HA dissociation from the cell surface (without affecting binding kinetics), revealing that CD44 activation state is a key regulator of HA retention. Competitive inhibition assay with fluorescein-conjugated HA, defined-size HA oligomers, kinetic binding/dissociation studies, monoclonal antibody activation The Journal of biological chemistry High 10871609
2003 CD44 undergoes ectodomain shedding catalyzed by ADAM10 (a disintegrin and metalloproteinase 10), which is augmented by CD44 ligation and Rac1-mediated cytoskeletal rearrangement. CD44 engagement activates Rac1, causing redistribution of CD44 to membrane ruffles at the leading edge; ADAM10 knockdown by RNAi suppresses CD44 cleavage. CD44 cleavage promotes tumor cell migration and invasion. Metalloproteinase inhibitors (KB-R7785, TIMP-1, TIMP-2), RNA interference of ADAM10, FRET-based visualization of active Rac1 in living cells, cell morphology/actin cytoskeleton analysis The Journal of biological chemistry High 14623895
2004 CD44 undergoes sequential proteolytic cleavages: (1) ectodomain shedding regulated by metalloproteinases and triggered by multiple stimuli, which controls cell attachment to and migration on HA matrix; (2) subsequent intramembranous cleavage by presenilin-dependent γ-secretase, generating a CD44 intracellular domain (CD44-ICD) that translocates to the nucleus and activates transcription. Biochemical analysis of cleavage fragments, γ-secretase inhibition, nuclear translocation assays Cancer science Medium 15596040
2006 CD44 functions as a primary phagocytic receptor: macrophages expressing CD44 efficiently engulf HA-coated beads and anti-CD44-opsonized erythrocytes via a mechanism involving Syk kinase, Rac1, and PI3-kinase, and inducing phagocyte oxidase activation. CD44-deficient macrophages cannot perform this phagocytosis, and the pathway is independent of Fc receptors. Hyaluronan-coated beads, anti-CD44-opsonized erythrocyte engulfment, CD44 knockout macrophages, immunoprecipitation, pharmacological inhibition (Syk, PI3K), genetic deletion Blood High 16455948
2008 CD44 directly associates with TLR2 upon stimulation by the TLR2 ligand zymosan and negatively regulates TLR-mediated NF-κB activation and proinflammatory cytokine production in vivo. The cytoplasmic domain of CD44 is required for this regulatory effect on TLR signaling. Co-immunoprecipitation of CD44 and TLR2, cytoplasmic domain deletion constructs, in vivo inflammation models, cytokine measurement Journal of immunology Medium 18322236
2010 CD44 promotes survival of effector Th1 cells by limiting Fas-mediated apoptosis, thereby enabling memory Th1 cell generation. CD44 ligation engages the PI3K-Akt signaling pathway in Th1 cells. This survival function is Th1-specific and is not observed in Th2, Th17, or CD8+ T cells despite equivalent CD44 expression. CD44-deficient mice, Th1/Th2/Th17/CD8+ T cell subset analysis, apoptosis assays, PI3K-Akt signaling pathway measurement Immunity High 20079666
2010 CD44 interacts with IQGAP1 (an actin-binding protein) via its intracellular C-terminus; an endogenous CD44-IQGAP1 complex was demonstrated in normal and transformed cell types, linking CD44 to cytoskeletal reorganization. Peptide-based pull-down with phosphorylated/non-phosphorylated CD44 C-terminal peptides, MALDI-TOF mass spectrometry identification, co-immunoprecipitation of endogenous complex IUBMB life Medium 21117172
2014 CD44 acts as a positive regulator of the Wnt receptor complex by physically associating with LRP6 upon Wnt stimulation and modulating LRP6 membrane localization. CD44 knockdown decreases, and overexpression increases, Wnt/β-catenin signaling activity. Epistasis experiments place CD44 function at the level of LRP6. CD44 regulates Wnt target gene expression (tcf-4 and en-2) in Xenopus brain development. Co-immunoprecipitation of CD44 and LRP6, CD44 knockdown/overexpression, Wnt reporter assay, epistasis analysis, CD44 morpholino knockdown in Xenopus laevis embryos Cell death and differentiation High 25301071
2014 CD44 signals through RhoA to regulate YAP expression and nuclear localization in the Hippo pathway. CD44 knockdown reduces RhoA expression, and constitutively active RhoA (RhoA-V14) rescues the YAP decrease caused by CD44 knockdown. CD44 knockdown also reduces expression of YAP target genes (CTGF, Cyr61, EDN1) and promotes apoptosis while inhibiting proliferation and migration. RNAi knockdown of CD44, overexpression of constitutively active RhoA, qRT-PCR of YAP targets, cell proliferation/apoptosis/migration assays Cellular signalling Medium 25101858
2015 CD44 regulates pancreatic cancer invasion through a CD44→Snail1→MT1-MMP (MMP14) axis: CD44 drives expression of the EMT transcription factor Snail1, which in turn regulates membrane-bound MT1-MMP expression required for invasion. Loss of CD44 reduces Snail1 and MT1-MMP levels and abolishes invasion in vitro and in vivo. CD44 knockdown/overexpression in pancreatic cancer cells, western blot for Snail1 and MT1-MMP, invasion assays, in vivo tumor models Molecular cancer research Medium 25566991
2017 Atomistic molecular dynamics simulations reveal that hyaluronan binds CD44's hyaluronan-binding domain via three topographically distinct binding modes. The crystallographic mode is the strongest; two metastable modes are more frequently observed in unbiased simulations. CD44 can diffuse along HA in a 1D manner when attached via weaker modes, potentially influencing CD44 aggregation kinetics relevant to signaling. Atomistic molecular dynamics simulations with multiple independent runs, comparison to X-ray crystallographic binding mode PLoS computational biology Low 28715483
2018 GPNMB attenuates astrocyte inflammatory responses through CD44: recombinant GPNMB reduces cytokine-induced iNOS, nitric oxide, ROS, and IL-6 in astrocytes, and this anti-inflammatory effect is abolished in CD44 knockout astrocytes, establishing CD44 as the required receptor for GPNMB-mediated neuroprotection. Recombinant GPNMB treatment, CD44 knockout primary astrocytes, qPCR, nitric oxide and ROS measurement, immunofluorescence Journal of neuroinflammation Medium 29519253
2020 CD44 mediates endocytosis of iron-bound hyaluronates, providing an alternative iron-uptake mechanism in mesenchymal-state cells. Internalized iron acts as a metal catalyst to demethylate repressive histone marks (H3K9me2/me3 and H3K27me3), thereby governing expression of mesenchymal genes and enabling epigenetic plasticity. CD44 expression is itself transcriptionally upregulated by nuclear iron through a positive feedback loop, in contrast to the negative iron regulation of transferrin receptor. Iron-bound hyaluronate endocytosis assays in tumorigenic cell lines and primary cancer cells, histone methylation profiling, small-molecule interference with iron homeostasis, EMT induction assays Nature chemistry High 32747755
2021 CD44 regulates membrane accumulation of COL17A1 (collagen XVII) in multilayered transformed epithelia. CD44 and COL17A1 accumulate in oncogene (RasV12, Src, ErbB2)-transformed epithelial cells, suppress mitochondrial ROS production, and thereby promote resistance to ferroptosis-mediated cell death during cell extrusion, enabling clonal expansion of transformed cells. Plasma membrane protein screening, COL17A1 knockout in RasV12 cells, metabolome analysis, ROS and mitochondrial membrane potential measurement, in vitro and in vivo multilayered epithelial models Current biology Medium 34087104
2012 CD44 is required for Kras-mediated MAPK signaling and lung adenocarcinoma formation in vivo: deletion of CD44 in a KrasG12D mouse model attenuates MAPK pathway activation, reduces tumor cell proliferation, decreases lung adenocarcinoma formation, and prolongs survival. Cre-mediated KrasG12D lung cancer mouse model with CD44 deletion, MAPK signaling assays, tumor burden quantification, survival analysis Oncogene Medium 23208496
1995 CD44 engagement (by HA or anti-CD44 mAbs) inhibits apoptosis induced by anti-CD3 mAbs and dexamethasone in T cells, but not UV-induced (p53-dependent) apoptosis, without upregulating Bcl-2 or affecting proliferation. This places CD44 as a survival signal that specifically counteracts TCR- and glucocorticoid-mediated apoptotic pathways. Anti-CD44 antibody and HA ligation, DNA fragmentation assay, apoptosis quantification, Bcl-2 expression analysis in 3DO T-cell line Blood Medium 7545465
2021 CD44 depletion (CRISPR/Cas9 KO) in GBM cells impairs proliferation (decreased Ki67, reduced CREB phosphorylation, elevated p16), decreases stemness, and induces senescence. γ-Secretase inhibition (DAPT, blocking CD44-ICD release) phenocopies some of these effects, suggesting CD44-ICD-dependent transcriptional regulation. CD44 KO also deregulates HAS2 and hyaluronan synthesis, and downregulation of HAS2 reduces CD44 protein levels, indicating a CD44/hyaluronan positive feedback circuit. CRISPR/Cas9 CD44 knockout, γ-secretase inhibitor DAPT, RNA sequencing, Ki67 staining, p16/CREB phosphorylation western blot, sphere formation assays Cancers Medium 35954411
2021 Androgen receptor (AR) directly represses CD44 transcription through a novel androgen response element silencer in the CD44 locus, as demonstrated by CRISPR-based mutagenesis of the ARE. AR ChIP-seq and transcriptomics confirmed CD44 as an AR-regulated gene, and AR and CD44 expression are inversely correlated in human bladder tumors. AR ChIP sequencing, transcriptomics, CRISPR mutagenesis of androgen response elements, pooled shRNA/ORF functional genomics screens, human tumor expression correlation Cancer research High 33687952

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 CD44 and its interaction with extracellular matrix. Advances in immunology 999 8379464
2015 Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer. Frontiers in immunology 668 25999946
1990 Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. The Journal of experimental medicine 596 2406365
1999 CD44 cell adhesion molecules. Molecular pathology : MP 540 10694938
2002 CD44 in cancer. Critical reviews in clinical laboratory sciences 462 12484499
1994 Expression and modulation of CD44 variant isoforms in humans. The Journal of cell biology 430 7507492
2001 A crucial role for CD44 in inflammation. Trends in molecular medicine 391 11325633
2010 CD44, a therapeutic target for metastasising tumours. European journal of cancer (Oxford, England : 1990) 379 20303742
2021 CD44: A Multifunctional Mediator of Cancer Progression. Biomolecules 349 34944493
1992 The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan. The Journal of cell biology 343 1370836
2000 Hyaluronan binding by cell surface CD44. The Journal of biological chemistry 340 10871609
2004 Mechanism and biological significance of CD44 cleavage. Cancer science 325 15596040
2009 Hyaluronan-CD44 Interactions in Cancer: Paradoxes and Possibilities. Clinical cancer research : an official journal of the American Association for Cancer Research 289 20008845
2006 Heparanase, hyaluronan, and CD44 in cancers: a breast carcinoma perspective. Cancer research 283 17079438
2020 CD44 regulates epigenetic plasticity by mediating iron endocytosis. Nature chemistry 231 32747755
2003 The liberation of CD44. The Journal of cell biology 214 12796473
2016 CD44: More than a mere stem cell marker. The international journal of biochemistry & cell biology 194 27640754
2022 The membrane receptor CD44: novel insights into metabolism. Trends in endocrinology and metabolism: TEM 176 35249813
2002 The hyaluronan receptor, CD44. The international journal of biochemistry & cell biology 171 11950588
1994 Expression of CD44 in human lung tumors. Cancer research 163 7509720
1997 CD44 in inflammation and metastasis. Glycoconjugate journal 162 9298694
1999 Activation and interaction of CD44 and hyaluronan in immunological systems. Journal of leukocyte biology 161 10449175
1996 Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. The Journal of cell biology 158 8601595
2018 The Role of CD44 and Cancer Stem Cells. Methods in molecular biology (Clifton, N.J.) 156 28986884
2008 Hyaluronan, CD44 and Emmprin: partners in cancer cell chemoresistance. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 153 18490190
1990 Hematopoietic progenitor cell expression of the H-CAM (CD44) homing-associated adhesion molecule. Blood 152 1688719
1997 CD44 and the adhesion of neoplastic cells. Molecular pathology : MP 151 9231152
2010 CD44 regulates survival and memory development in Th1 cells. Immunity 149 20079666
1991 Expression of CD44 is repressed in neuroblastoma cells. Molecular and cellular biology 146 1922057
2015 CD44: molecular interactions, signaling and functions in the nervous system. Frontiers in cellular neuroscience 140 25999819
2018 The glycoprotein GPNMB attenuates astrocyte inflammatory responses through the CD44 receptor. Journal of neuroinflammation 138 29519253
2022 CD44-Targeted Nanocarrier for Cancer Therapy. Frontiers in pharmacology 135 35431911
2014 CD44 functions in Wnt signaling by regulating LRP6 localization and activation. Cell death and differentiation 135 25301071
1998 The CD44 protein family. The international journal of biochemistry & cell biology 124 9611772
2016 The role of CD44 in glioblastoma multiforme. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 120 27578526
2003 Engagement of CD44 promotes Rac activation and CD44 cleavage during tumor cell migration. The Journal of biological chemistry 120 14623895
2006 CD44 is a phagocytic receptor. Blood 117 16455948
2004 Hyaluronan and CD44: modulators of chondrocyte metabolism. Clinical orthopaedics and related research 113 15480059
1998 CD44 structure and function. Frontiers in bioscience : a journal and virtual library 109 9634544
2012 Regulation of ABCB1/PGP1-catalysed auxin transport by linker phosphorylation. The EMBO journal 108 22549467
2015 Interactions between CD44 and Hyaluronan in Leukocyte Trafficking. Frontiers in immunology 107 25741341
1995 CD44 isoforms during differentiation and development. BioEssays : news and reviews in molecular, cellular and developmental biology 107 7535522
2003 CD44 and its partners in metastasis. Clinical & experimental metastasis 98 12741678
2020 The role of CD44 in pathological angiogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 95 32830349
2003 CD44 in rheumatoid arthritis. Arthritis research & therapy 92 12723975
2014 Perspectives of CD44 targeting therapies. Archives of toxicology 90 25472903
2012 Role of CD44 in tumour progression and strategies for targeting. Journal of drug targeting 90 22758394
2012 Peptidoglycan-modifying enzyme Pgp1 is required for helical cell shape and pathogenicity traits in Campylobacter jejuni. PLoS pathogens 86 22457624
2015 Expression of CD44 in pancreatic cancer and its significance. International journal of clinical and experimental pathology 84 26261555
1995 CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis. Blood 84 7545465
2020 Role of CD44 in breast cancer. Breast disease 83 31839599
1993 CD44 expression on murine tissues. Journal of cell science 82 8505366
2021 The role of CD44 in cancer chemoresistance: A concise review. European journal of pharmacology 81 33961871
2012 CD44 in human glioma correlates with histopathological grade and cell migration. Pathology international 79 22726066
2008 CD44 suppresses TLR-mediated inflammation. Journal of immunology (Baltimore, Md. : 1950) 78 18322236
2015 CD44 regulates pancreatic cancer invasion through MT1-MMP. Molecular cancer research : MCR 77 25566991
2020 Understanding Hyaluronan Receptor (CD44) Interaction, HA-CD44 Activated Potential Targets in Cancer Therapeutics. Advanced pharmaceutical bulletin 75 34513617
2006 CD44 and hematologic malignancies. Cellular & molecular immunology 73 17092433
2019 CD44(+) tumor cells promote early angiogenesis in head and neck squamous cell carcinoma. Cancer letters 72 31593802
2009 Rheostatic signaling by CD44 and hyaluronan. Cellular signalling 69 19174187
1995 CD44 in colon cancer. European journal of cancer (Oxford, England : 1990) 69 7577002
2018 Hyaluronic acid, CD44 and RHAMM regulate myoblast behavior during embryogenesis. Matrix biology : journal of the International Society for Matrix Biology 65 30130585
1999 Signal transduction via CD44: role of plasma membrane microdomains. Leukemia & lymphoma 62 10609783
2006 Expression of CD44 in rat hepatic progenitor cells. Journal of hepatology 61 16580085
2011 CD44 in hematological neoplasias. Annals of hematology 60 21258793
2014 HAS2 and CD44 in breast tumorigenesis. Advances in cancer research 57 25081531
2014 CD44 acts through RhoA to regulate YAP signaling. Cellular signalling 57 25101858
2007 CD44 involvement in autoimmune inflammations: the lesson to be learned from CD44-targeting by antibody or from knockout mice. Annals of the New York Academy of Sciences 54 17911438
2019 Involvement of hyaluronan and CD44 in cancer and viral infections. Cellular signalling 52 31654718
2011 CD44-SLC1A2 gene fusions in gastric cancer. Science translational medicine 52 21471434
2002 CD44 expression in human gliomas. Journal of surgical oncology 51 11754374
2017 CD44+ fibroblasts increases breast cancer cell survival and drug resistance via IGF2BP3-CD44-IGF2 signalling. Journal of cellular and molecular medicine 50 28523716
2008 Hyaluronan, CD44, and cyclooxygenase-2 in colon cancer. Connective tissue research 50 18661347
2003 The hyaluronic acid receptor (CD44) is expressed in bovine oocytes and early stage embryos. Theriogenology 49 14580646
1994 CD44 isoforms in metastatic cancer. Invasion & metastasis 49 7544777
2018 CD44 glycoprotein in cancer: a molecular conundrum hampering clinical applications. Clinical proteomics 48 29983670
2003 Hyaluronan, CD44 and versican in epidermal keratinocyte tumours. The British journal of dermatology 47 12534600
2018 CD44 is overexpressed and correlated with tumor progression in gallbladder cancer. Cancer management and research 46 30288117
2015 Modulation of CD44 Activity by A6-Peptide. Frontiers in immunology 45 25870596
2012 CD44 promotes Kras-dependent lung adenocarcinoma. Oncogene 45 23208496
1996 CD44 and hyaluronan binding by human myeloid cells. Leukemia & lymphoma 45 9172805
1991 Full length and alternatively spliced pgp1 transcripts in multidrug-resistant Chinese hamster lung cells. The Journal of biological chemistry 44 1671863
2019 Structure, function and role of CD44 in neoplasia. Journal of oral and maxillofacial pathology : JOMFP 43 31516234
2015 Expression and Function of CD44 in Epithelial Ovarian Carcinoma. Biomolecules 43 26569327
2002 CD44 expression in IgA nephropathy. American journal of kidney diseases : the official journal of the National Kidney Foundation 41 11840384
2023 A Narrative Review on CD44's Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence. Cancers 40 37835592
2002 CD44: functional relevance to inflammation and malignancy. Histology and histopathology 40 12168806
1999 Expression of CD44 variants in osteosarcoma. Journal of cancer research and clinical oncology 40 10541973
2017 Atomistic fingerprint of hyaluronan-CD44 binding. PLoS computational biology 39 28715483
2021 The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia. Current biology : CB 38 34087104
2021 MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44. Scientific reports 34 33911148
2010 Proteomic identification of CD44 interacting proteins. IUBMB life 34 21117172
2021 Androgen Receptor Regulates CD44 Expression in Bladder Cancer. Cancer research 33 33687952
2014 CD44 clustering is involved in monocyte differentiation. Acta biochimica et biophysica Sinica 32 24850301
2024 CD44 and its implication in neoplastic diseases. MedComm 31 38783892
2017 Whether CD44 is an applicable marker for glioma stem cells. American journal of translational research 31 29218080
2014 PTK7 regulates Id1 expression in CD44-high glioma cells. Neuro-oncology 31 25204555
2012 CD44(+) cells have cancer stem cell-like properties in nasopharyngeal carcinoma. International forum of allergy & rhinology 31 22887934
2022 CD44 Depletion in Glioblastoma Cells Suppresses Growth and Stemness and Induces Senescence. Cancers 30 35954411
2018 The role of CD44, hyaluronan and NHE1 in cardiac remodeling. Life sciences 30 30089233

Missed literature

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