CD44
| View/Edit Human | View/Edit Mouse |
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 gene on chromosome 11.[5] CD44 has been referred to as HCAM (homing cell adhesion molecule), Pgp-1 (phagocytic glycoprotein-1), Hermes antigen, lymphocyte homing receptor, ECM-III, and HUTCH-1.
Tissue distribution and isoforms
CD44 is expressed in a large number of mammalian cell types. The standard isoform, designated CD44s, comprising exons 1–5 and 16–20 is expressed in most cell types. CD44 splice variants containing variable exons are designated CD44v. Some epithelial cells also express a larger isoform (CD44E), which includes exons v8–10.[6]
Function
CD44 participates in a wide variety of cellular functions including
CD44 is a receptor for hyaluronic acid[7] and internalizes metals bound to hyaluronic acid[8][9] and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). CD44 function is controlled by its posttranslational modifications. One critical modification involves discrete sialofucosylations rendering the selectin-binding glycoform of CD44 called HCELL (for Hematopoietic Cell E-selectin/L-selectin Ligand).[10] (see below)
Transcripts for this
CD44 gene
HCELL
The HCELL glycoform was originally discovered on human hematopoietic stem cells and leukemic blasts,
Clinical significance
The protein is a determinant for the Indian blood group system.
- CD44, along with .
- CD44 expression is an indicative marker for effector-memory T-cells. Memory cell proliferation (activation) can also be assayed in vitro with CFSE chemical tagging.
In addition, variations in CD44 are reported as cell surface markers for some breast and prostate
Endometrial cells in women with endometriosis demonstrate increased expression of splice variants of CD44, and increased adherence to peritoneal cells.[24]
CD44 variant
CD44 in cancer
CD44 is a multistructural and multifunctional
High levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia.
In many cancers (renal cancer and non-Hodgkin's lymphomas are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome.[29] On the contrary, in some neoplasms CD44 upregulation is associated with a favorable outcome. This is true of prostate cancer, where the transcript variant CD44v5 (includes the fifth 'v5' exon) is associated with better prognosis (increased time to recurrence following surgery).[30][29] In prostate cancer, the exclusion of the v5 exon through alternative splicing was associated with the presence of RNA binding protein KHDRBS1 and became included in the presence of increased YTHDC1 or metadherin expression.[30]
In other cases different research groups analyzing the same neoplastic disease reached contradictory conclusions regarding the correlation between CD44 expression and disease prognosis, possibly due to differences in methodology. These problems must be resolved before applying anti-CD44 therapy to human cancers.[29]
Interactions
CD44 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000026508 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005087 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2454887.
- PMID 10694938.
- S2CID 8217636.
- PMID 32747755.
- PMID 37100912.
- ^ PMID 7524735.
- ^ S2CID 31373618.
- ^ PMID 15994957.
- PMID 11023510.
- ^ S2CID 5095656.
- PMID 11402070.
- PMID 16565092.
- ^ S2CID 23662591.
- ^ PMID 17135256.
- ^ PMID 18375392.
- PMID 19594629.
- ^ PMID 19004834.
- PMID 17179981.
- PMID 14614016.
- PMID 19200980.
- PMID 19507218.
- PMID 12371152.
- PMID 21116281.
- S2CID 21251441.
- ^ S2CID 30019668.
- ^ PMID 31450747.
- PMID 12748184.
- PMID 25572402.
- PMID 23589287.
- PMID 1730778.
- ^ PMID 9573028.
- S2CID 8217636.
- PMID 8576267.
- S2CID 11548419.
- PMID 11084024.
- PMID 17045821.
Further reading
- Sackstein R (Jul 2011). "The biology of CD44 and HCELL in hematopoiesis: the 'step 2-bypass pathway' and other emerging perspectives". Current Opinion in Hematology. 18 (4): 239–48. PMID 21546828.
- Sackstein R (Jul 2009). "Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration". Immunological Reviews. 230 (1): 51–74. PMID 19594629.
- Sackstein R (May 2004). "The bone marrow is akin to skin: HCELL and the biology of hematopoietic stem cell homing". The Journal of Investigative Dermatology. 122 (5): 1061–9. PMID 15140204.
- Konstantopoulos K, Thomas SN (2009). "Cancer cells in transit: the vascular interactions of tumor cells". Annual Review of Biomedical Engineering. 11: 177–202. PMID 19413512.
- Günthert U (1993). "CD44: A Multitude of Isoforms with Diverse Functions". Adhesion in Leukocyte Homing and Differentiation (PDF). Current Topics in Microbiology and Immunology. Vol. 184. pp. 47–63. PMID 7508842.
- Yasuda M, Nakano K, Yasumoto K, Tanaka Y (2003). "CD44: functional relevance to inflammation and malignancy". Histology and Histopathology. 17 (3): 945–50. PMID 12168806.
- Sun CX, Robb VA, Gutmann DH (Nov 2002). "Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation". Journal of Cell Science. 115 (Pt 21): 3991–4000. S2CID 14243743.
- Ponta H, Sherman L, Herrlich PA (Jan 2003). "CD44: from adhesion molecules to signalling regulators". Nature Reviews Molecular Cell Biology. 4 (1): 33–45. S2CID 19495756.
- Martin TA, Harrison G, Mansel RE, Jiang WG (May 2003). "The role of the CD44/ezrin complex in cancer metastasis". Critical Reviews in Oncology/Hematology. 46 (2): 165–86. PMID 12711360.
External links
- Indian blood group system at NIH
- Articles at IHOP.
- Human CD44 genome location and CD44 gene details page in the UCSC Genome Browser.
PDB gallery | |
|---|---|
|
