View source for CD44

{{Short description|Cell-surface glycoprotein}}
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{{Infobox_gene}}
The '''CD44 antigen''' is a [[cell (biology)|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.<ref name="pmid2454887">{{cite journal | vauthors = Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, Fabre JW, Anstee DJ | title = The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene | journal = Immunology | volume = 64 | issue = 1 | pages = 37–43 | date = May 1988 | pmid = 2454887 | pmc = 1385183 }}</ref> 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 [[protein isoform|isoform]], designated CD44s, comprising [[exon]]s 1–5 and 16–20 is expressed in most cell types. CD44 splice variants containing variable exons are designated CD44v.  Some [[epithelium|epithelial cells]] also express a larger isoform (CD44E), which includes exons v8–10.<ref name="pmid10694938">{{cite journal | vauthors = Goodison S, Urquidi V, Tarin D | title = CD44 cell adhesion molecules | journal = Molecular Pathology | volume = 52 | issue = 4 | pages = 189–196 | date = August 1999 | pmid = 10694938 | pmc = 395698 | doi = 10.1136/mp.52.4.189 }}</ref>

== Function ==

CD44 participates in a wide variety of cellular functions including [[lymphocyte]] activation,  recirculation and homing, [[hematopoiesis]], and [[tumor]] [[metastasis]].

CD44 is a receptor for [[hyaluronic acid]]<ref>{{cite journal | vauthors = Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B | title = CD44 is the principal cell surface receptor for hyaluronate | journal = Cell | volume = 61 | issue = 7 | pages = 1303–1313 | date = June 1990 | pmid = 1694723 | doi = 10.1016/0092-8674(90)90694-a | s2cid = 8217636 }}</ref> and internalizes metals bound to hyaluronic acid<ref>{{cite journal | vauthors = Müller S, Sindikubwabo F, Cañeque T, Lafon A, Versini A, Lombard B, Loew D, Wu TD, Ginestier C, Charafe-Jauffret E, Durand A, Vallot C, Baulande S, Servant N, Rodriguez R | title = CD44 regulates epigenetic plasticity by mediating iron endocytosis | journal = Nature Chemistry | volume = 12 | issue = 10 | pages = 929–938 | date = October 2020 | pmid = 32747755 | pmc = 7612580 | doi = 10.1038/s41557-020-0513-5 | bibcode = 2020NatCh..12..929M }}</ref><ref>{{cite journal | vauthors = Solier S, Müller S, Cañeque T, Versini A, Mansart A, Sindikubwabo F, Baron L, Emam L, Gestraud P, Pantoș GD, Gandon V, Gaillet C, Wu TD, Dingli F, Loew D, Baulande S, Durand S, Sencio V, Robil C, Trottein F, Péricat D, Näser E, Cougoule C, Meunier E, Bègue AL, Salmon H, Manel N, Puisieux A, Watson S, Dawson MA, Servant N, Kroemer G, Annane D, Rodriguez R | title = A druggable copper-signalling pathway that drives inflammation | journal = Nature | volume = 617 | issue = 7960 | pages = 386–394 | date = May 2023 | pmid = 37100912 | pmc = 10131557 | doi = 10.1038/s41586-023-06017-4 | bibcode = 2023Natur.617..386S }}</ref> and can also interact with other [[ligand]]s, such as [[osteopontin]], [[collagen]]s, and [[matrix metalloproteinase]]s (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).<ref name="pmid7524735"/> (see below)

Transcripts for this [[gene]] undergo complex [[alternative splicing]] that results in many functionally distinct [[isoform]]s; however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis.  Splice variants of CD44 on colon cancer cells display sialofucosylated HCELL glycoforms that serve as P-, L-, and E-selectin ligands and fibrin, but not fibrinogen, receptors under hemodynamic flow conditions pertinent to the process of cancer metastasis.<ref name="pmid18234849"/><ref name="pmid15994957"/>

CD44 gene [[Transcription (genetics)|transcription]] is at least in part activated by [[beta-catenin]] and [[Wnt signaling pathway|Wnt signalling]] (also linked to tumour development).

===HCELL===
HCELL (Hematopoietic Cell E-/L-selectin Ligand) is a specialized glycoform of the CD44 protein that functions as a critical [[adhesion molecule]] in [[hematopoietic]]<ref name="pmid21546828">{{cite journal | vauthors = Sackstein R | title = The biology of CD44 and HCELL in hematopoiesis: the 'step 2-bypass pathway' and other emerging perspectives | journal = Current Opinion in Hematology | volume = 18 | issue = 4 | pages = 239–48 | date = July 2011 | pmid = 21546828 | pmc = 3145154 | doi = 10.1097/MOH.0b013e3283476140 | url = }}</ref> and immune processes.<ref name="pmid28515724">{{cite journal | vauthors = Ali AJ, Abuelela AF, Merzaban JS | title = An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells | journal = Frontiers in Immunology | volume = 8 | issue = | pages = 492 | date = 2017 | pmid = 28515724 | pmc = 5413510 | doi = 10.3389/fimmu.2017.00492 | doi-access = free | url = }}</ref> It is distinguished by unique post-translational modifications that enable potent binding to [[E-selectin]] and [[L-selectin]], guiding cell migration and homing.<ref name="pmid21257905">{{cite journal | vauthors = Thankamony SP, Sackstein R | title = Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 6 | pages = 2258–63 | date = February 2011 | pmid = 21257905 | pmc = 3038774 | doi = 10.1073/pnas.1018064108 | doi-access = free | bibcode = 2011PNAS..108.2258T | url = }}</ref>

The HCELL glycoform was originally discovered on human hematopoietic stem cells and leukemic blasts,<ref name="pmid7524735">{{cite journal | vauthors = Oxley SM, Sackstein R | title = Detection of an L-selectin ligand on a hematopoietic progenitor cell line | journal = Blood | volume = 84 | issue = 10 | pages = 3299–3306 | date = November 1994 | pmid = 7524735 | doi = 10.1182/blood.V84.10.3299.3299 | doi-access = free }}</ref><ref name="pmid11023510">{{cite journal | vauthors = Sackstein R, Dimitroff CJ | title = A hematopoietic cell L-selectin ligand that is distinct from PSGL-1 and displays N-glycan-dependent binding activity | journal = Blood | volume = 96 | issue = 8 | pages = 2765–2774 | date = October 2000 | pmid = 11023510 | doi = 10.1182/blood.V96.8.2765 }}</ref><ref name="pmid18193058">{{cite journal | vauthors = Sackstein R, Merzaban JS, Cain DW, Dagia NM, Spencer JA, Lin CP, Wohlgemuth R | title = Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone | journal = Nature Medicine | volume = 14 | issue = 2 | pages = 181–187 | date = February 2008 | pmid = 18193058 | doi = 10.1038/nm1703 | s2cid = 5095656 }}</ref><ref name="pmid11402070">{{cite journal | vauthors = Dimitroff CJ, Lee JY, Rafii S, Fuhlbrigge RC, Sackstein R | title = CD44 is a major E-selectin ligand on human hematopoietic progenitor cells | journal = The Journal of Cell Biology | volume = 153 | issue = 6 | pages = 1277–1286 | date = June 2001 | pmid = 11402070 | pmc = 2192031 | doi = 10.1083/jcb.153.6.1277 }}</ref> and was subsequently identified on cancer cells.<ref name="pmid15994957">{{cite journal | vauthors = Hanley WD, Burdick MM, Konstantopoulos K, Sackstein R | title = CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity | journal = Cancer Research | volume = 65 | issue = 13 | pages = 5812–5817 | date = July 2005 | pmid = 15994957 | doi = 10.1158/0008-5472.CAN-04-4557 | doi-access = free }}</ref><ref name="pmid16565092">{{cite journal | vauthors = Burdick MM, Chu JT, Godar S, Sackstein R | title = HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma cells | journal = The Journal of Biological Chemistry | volume = 281 | issue = 20 | pages = 13899–13905 | date = May 2006 | pmid = 16565092 | doi = 10.1074/jbc.M513617200 | doi-access = free }}</ref><ref name="pmid16352650">{{cite journal | vauthors = Hanley WD, Napier SL, Burdick MM, Schnaar RL, Sackstein R, Konstantopoulos K | title = Variant isoforms of CD44 are P- and L-selectin ligands on colon carcinoma cells | journal = FASEB Journal | volume = 20 | issue = 2 | pages = 337–339 | date = February 2006 | pmid = 16352650 | doi = 10.1096/fj.05-4574fje | s2cid = 23662591 | doi-access = free }}</ref><ref name="pmid17135256">{{cite journal | vauthors = Napier SL, Healy ZR, Schnaar RL, Konstantopoulos K | title = Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44v and alternative sialofucosylated selectin ligands | journal = The Journal of Biological Chemistry | volume = 282 | issue = 6 | pages = 3433–3441 | date = February 2007 | pmid = 17135256 | doi = 10.1074/jbc.M607219200 | doi-access = free }}</ref><ref name="pmid18375392">{{cite journal | vauthors = Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K | title = Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow | journal = The Journal of Biological Chemistry | volume = 283 | issue = 23 | pages = 15647–15655 | date = June 2008 | pmid = 18375392 | pmc = 2414264 | doi = 10.1074/jbc.M800543200 | doi-access = free }}</ref> HCELL functions as a "bone [[Homing (hematopoietic)|homing]] receptor", directing migration of human hematopoietic stem cells and [[mesenchymal stem cells]] to bone marrow.<ref name="pmid18193058"/>   Ex vivo glycan engineering of the surface of live cells has been used to enforce HCELL expression on any cell that expresses CD44.<ref name="pmid19594629">{{cite journal | vauthors = Sackstein R | title = Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration | journal = Immunological Reviews | volume = 230 | issue = 1 | pages = 51–74 | date = July 2009 | pmid = 19594629 | pmc = 4306344 | doi = 10.1111/j.1600-065X.2009.00792.x }}</ref> CD44 glycosylation also directly controls its binding capacity to fibrin and immobilized fibrinogen.<ref name="pmid18234849">{{cite journal | vauthors = Alves CS, Burdick MM, Thomas SN, Pawar P, Konstantopoulos K | title = The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion | journal = American Journal of Physiology. Cell Physiology | volume = 294 | issue = 4 | pages = C907–C916 | date = April 2008 | pmid = 18234849 | doi = 10.1152/ajpcell.00463.2007 | s2cid = 31373618 }}</ref><ref name="pmid19004834">{{cite journal | vauthors = Alves CS, Yakovlev S, Medved L, Konstantopoulos K | title = Biomolecular characterization of CD44-fibrin(ogen) binding: distinct molecular requirements mediate binding of standard and variant isoforms of CD44 to immobilized fibrin(ogen) | journal = The Journal of Biological Chemistry | volume = 284 | issue = 2 | pages = 1177–1189 | date = January 2009 | pmid = 19004834 | pmc = 2613610 | doi = 10.1074/jbc.M805144200 | doi-access = free }}</ref>

== Clinical significance ==

The protein is a determinant for the [[Indian blood group system]].
* CD44, along with [[CD25]], is used to track early [[T cell]] development in the [[thymus]].
* CD44 expression is an indicative marker for effector-memory T-cells. Memory cell proliferation (activation) can also be assayed ''in vitro'' with [[Carboxyfluorescein succinimidyl ester|CFSE]] chemical tagging.
* CD44 is a biomarker of [[cancer stem cells]],<ref name="pmid26136504">{{cite journal | vauthors = Yan Y, Zuo X, Wei D | title = Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target | journal = Stem Cells Translational Medicine | volume = 4 | issue = 9 | pages = 1033–1043 | date = September 2015 | pmid = 26136504 | pmc = 4542874 | doi = 10.5966/sctm.2015-0048 }}</ref> and these cells can potentially be targeted] with novel therapies.<ref name="pmid32296030">{{cite journal | vauthors = Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, Zhang G, Wang X, Dong Z, Chen F, Cui H | title = Targeting cancer stem cell pathways for cancer therapy | journal = Signal Transduction and Targeted Therapy | volume = 5 | issue = 1 | pages = 8 | date = February 2020 | pmid = 32296030 | pmc = 7005297 | doi = 10.1038/s41392-020-0110-5 }}</ref>

In addition, variations in CD44 are reported as cell surface markers for some breast and prostate [[cancer stem cells]]. In breast cancer research CD44+/CD24- expression is commonly used as a marker for breast CSCs and is used to sort breast cancer cells into a population enriched in cells with stem-like characteristics<ref name="pmid17179981">{{cite journal | vauthors = Li F, Tiede B, Massagué J, Kang Y | title = Beyond tumorigenesis: cancer stem cells in metastasis | journal = Cell Research | volume = 17 | issue = 1 | pages = 3–14 | date = January 2007 | pmid = 17179981 | doi = 10.1038/sj.cr.7310118 | doi-access = free }}</ref> and has been seen as an indicator of increased survival time in [[epithelial]] [[ovarian cancer]] patients.<ref name="pmid14614016">{{cite journal | vauthors = Sillanpää S, Anttila MA, Voutilainen K, Tammi RH, Tammi MI, Saarikoski SV, Kosma VM | title = CD44 expression indicates favorable prognosis in epithelial ovarian cancer | journal = Clinical Cancer Research | volume = 9 | issue = 14 | pages = 5318–5324 | date = November 2003 | pmid = 14614016 | url = http://clincancerres.aacrjournals.org/content/9/14/5318.long }}</ref>

Endometrial cells in women with [[endometriosis]] demonstrate increased expression of splice variants of CD44, and increased adherence to peritoneal cells.<ref name="pmid19200980">{{cite journal | vauthors = Griffith JS, Liu YG, Tekmal RR, Binkley PA, Holden AE, Schenken RS | title = Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants | journal = Fertility and Sterility | volume = 93 | issue = 6 | pages = 1745–1749 | date = April 2010 | pmid = 19200980 | pmc = 2864724 | doi = 10.1016/j.fertnstert.2008.12.012 }}</ref>

CD44 variant [[isoform]]s are also relevant to the progression of [[head and neck cancer|head and neck squamous cell carcinoma]].<ref name="Wang2009">{{cite journal | vauthors = Wang SJ, Wong G, de Heer AM, Xia W, Bourguignon LY | title = CD44 variant isoforms in head and neck squamous cell carcinoma progression | journal = The Laryngoscope | volume = 119 | issue = 8 | pages = 1518–1530 | date = August 2009 | pmid = 19507218 | pmc = 2718060 | doi = 10.1002/lary.20506 }}</ref><ref name="Assim2003">{{cite journal | vauthors = Assimakopoulos D, Kolettas E, Patrikakos G, Evangelou A | title = The role of CD44 in the development and prognosis of head and neck squamous cell carcinomas | journal = Histology and Histopathology | volume = 17 | issue = 4 | pages = 1269–1281 | date = October 2002 | pmid = 12371152 | doi = 10.14670/HH-17.1269 }}</ref>

[[Monoclonal antibodies]] against CD44 variants include [[bivatuzumab]] for v6.

== CD44 in cancer ==

CD44 is a multistructural and multifunctional [[Cell adhesion molecule|cell surface molecule]] involved in [[Cell growth|cell proliferation]], [[Cellular differentiation|cell differentiation]], [[cell migration]], [[angiogenesis]], presentation of [[cytokines]], [[chemokines]], and growth factors to the corresponding [[Receptor (biochemistry)|receptors]], and docking of [[protease]]s at the [[cell membrane]], as well as in signaling for [[Apoptosis|cell survival]]. All these biological properties are essential to the physiological activities of normal cells, but they are also associated with the pathologic activities of [[cancer cell]]s. Experiments in animals have shown that targeting of CD44 by [[Antibody|antibodies]], [[Antisense therapy|antisense]] oligonucleotides, and CD44-soluble proteins markedly reduces the malignant activities of various [[neoplasm]]s, stressing the therapeutic potential of anti-CD44 agents.

High levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia.<ref>{{cite journal | vauthors = Quéré R, Andradottir S, Brun AC, Zubarev RA, Karlsson G, Olsson K, Magnusson M, Cammenga J, Karlsson S | title = High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event | journal = Leukemia | volume = 25 | issue = 3 | pages = 515–526 | date = March 2011 | pmid = 21116281 | pmc = 3072510 | doi = 10.1038/leu.2010.281 }}</ref> Furthermore, because [[alternative splicing]] and [[posttranslational modification]]s generate many different CD44 sequences, including, perhaps, tumor-specific sequences, the production of anti-CD44 tumor-specific agents may be a realistic therapeutic approach.<ref>{{cite journal | vauthors = Eibl RH, Pietsch T, Moll J, Skroch-Angel P, Heider KH, von Ammon K, Wiestler OD, Ponta H, Kleihues P, Herrlich P | title = Expression of variant CD44 epitopes in human astrocytic brain tumors | journal = Journal of Neuro-Oncology | volume = 26 | issue = 3 | pages = 165–170 | date = December 1995 | pmid = 8750182 | doi = 10.1007/bf01052619 | s2cid = 21251441 }}</ref>

In many cancers ([[Renal cell carcinoma|renal cancer]] and [[Non-Hodgkin lymphoma|non-Hodgkin's lymphomas]] are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome.<ref name=":0" /> On the contrary, in some neoplasms CD44 [[Downregulation and upregulation|upregulation]] is associated with a favorable outcome. This is true of [[prostate cancer]], where the [[Alternative splicing|transcript variant]] CD44v5 (includes the fifth 'v5' exon) is associated with better prognosis (increased time to recurrence following surgery).<ref name=":1">{{cite journal | vauthors = Luxton HJ, Simpson BS, Mills IG, Brindle NR, Ahmed Z, Stavrinides V, Heavey S, Stamm S, Whitaker HC | title = The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing | journal = Cancers | volume = 11 | issue = 9 | page = 1233 | date = August 2019 | pmid = 31450747 | pmc = 6770463 | doi = 10.3390/cancers11091233 | doi-access = free }}</ref><ref name=":0" /> 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 [[MTDH|metadherin]] expression.<ref name=":1" />

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.<ref name=":0">{{cite journal | vauthors = Naor D, Nedvetzki S, Golan I, Melnik L, Faitelson Y | title = CD44 in cancer | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 39 | issue = 6 | pages = 527–579 | date = November 2002 | pmid = 12484499 | doi = 10.1080/10408360290795574 | s2cid = 30019668 }}</ref>

== Interactions ==

CD44 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[ARHGEF1]],<ref name="pmid12748184">{{cite journal | vauthors = Bourguignon LY, Singleton PA, Zhu H, Diedrich F | title = Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29420–29434 | date = August 2003 | pmid = 12748184 | doi = 10.1074/jbc.M301885200 | doi-access = free }}</ref>
* [[Ezrin]], via [[PIP2]],<ref>{{cite journal | vauthors = Chen X, Khajeh JA, Ju JH, Gupta YK, Stanley CB, Do C, Heller WT, Aggarwal AK, Callaway DJ, Bu Z | title = Phosphatidylinositol 4,5-bisphosphate clusters the cell adhesion molecule CD44 and assembles a specific CD44-Ezrin heterocomplex, as revealed by small angle neutron scattering | journal = The Journal of Biological Chemistry | volume = 290 | issue = 10 | pages = 6639–6652 | date = March 2015 | pmid = 25572402 | pmc = 4358296 | doi = 10.1074/jbc.M114.589523 | doi-access = free }}</ref>
* [[Epidermal Growth Factor Receptor]] (Hyaluronan-dependent),<ref>{{cite journal | vauthors = Midgley AC, Rogers M, Hallett MB, Clayton A, Bowen T, Phillips AO, Steadman R | title = Transforming growth factor-β1 (TGF-β1)-stimulated fibroblast to myofibroblast differentiation is mediated by hyaluronan (HA)-facilitated epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid rafts | journal = The Journal of Biological Chemistry | volume = 288 | issue = 21 | pages = 14824–14838 | date = May 2013 | pmid = 23589287 | pmc = 3663506 | doi = 10.1074/jbc.M113.451336 | doi-access = free }}</ref>
* [[Fibrin]] and immobilized [[fibrinogen]],<ref name="pmid18234849"/><ref name="pmid19004834"/>
* [[Fibronectin]],<ref name="pmid1730778">{{cite journal | vauthors = Jalkanen S, Jalkanen M | title = Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin | journal = The Journal of Cell Biology | volume = 116 | issue = 3 | pages = 817–825 | date = February 1992 | pmid = 1730778 | pmc = 2289325 | doi = 10.1083/jcb.116.3.817 }}</ref>
* [[FYN]],<ref name="pmid9573028">{{cite journal | vauthors = Ilangumaran S, Briol A, Hoessli DC | title = CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes | journal = Blood | volume = 91 | issue = 10 | pages = 3901–3908 | date = May 1998 | pmid = 9573028 | doi = 10.1182/blood.V91.10.3901 | doi-access = free }}</ref>
* [[Hyaluronan]],<ref name="pmid1694723">{{cite journal | vauthors = Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B | title = CD44 is the principal cell surface receptor for hyaluronate | journal = Cell | volume = 61 | issue = 7 | pages = 1303–1313 | date = June 1990 | pmid = 1694723 | doi = 10.1016/0092-8674(90)90694-A | s2cid = 8217636 }}</ref>
* [[Lck]],<ref name=pmid9573028/><ref name="pmid8576267">{{cite journal | vauthors = Taher TE, Smit L, Griffioen AW, Schilder-Tol EJ, Borst J, Pals ST | title = Signaling through CD44 is mediated by tyrosine kinases. Association with p56lck in T lymphocytes | journal = The Journal of Biological Chemistry | volume = 271 | issue = 5 | pages = 2863–2867 | date = February 1996 | pmid = 8576267 | doi = 10.1074/jbc.271.5.2863 | doi-access = free }}</ref>
* [[Osteopontin]]<ref name="Zohar">{{cite journal | vauthors = Zohar R, Suzuki N, Suzuki K, Arora P, Glogauer M, McCulloch CA, Sodek J | title = Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration | journal = Journal of Cellular Physiology | volume = 184 | issue = 1 | pages = 118–130 | date = July 2000 | pmid = 10825241 | doi = 10.1002/(SICI)1097-4652(200007)184:1<118::AID-JCP13>3.0.CO;2-Y | s2cid = 11548419 }}</ref>
* [[Selectins]],<ref name="pmid16352650"/><ref name="pmid17135256"/><ref name="pmid18375392"/> and
* [[Src (gene)|Src]],<ref name="pmid11084024">{{cite journal | vauthors = Bourguignon LY, Zhu H, Shao L, Chen YW | title = CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration | journal = The Journal of Biological Chemistry | volume = 276 | issue = 10 | pages = 7327–7336 | date = March 2001 | pmid = 11084024 | doi = 10.1074/jbc.M006498200 | doi-access = free }}</ref>
* [[CD74]].<ref name="Xuerong">{{cite journal | vauthors = Shi X, Leng L, Wang T, Wang W, Du X, Li J, McDonald C, Chen Z, Murphy JW, Lolis E, Noble P, Knudson W, Bucala R | title = CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex | journal = Immunity | volume = 25 | issue = 4 | pages = 595–606 | date = October 2006 | pmid = 17045821 | pmc = 3707630 | doi = 10.1016/j.immuni.2006.08.020 }}</ref>
{{Div col end}}

== References ==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Sackstein R | title = The biology of CD44 and HCELL in hematopoiesis: the 'step 2-bypass pathway' and other emerging perspectives | journal = Current Opinion in Hematology | volume = 18 | issue = 4 | pages = 239–248 | date = July 2011 | pmid = 21546828 | pmc = 3145154 | doi = 10.1097/MOH.0b013e3283476140 }}
* {{cite journal | vauthors = Sackstein R | title = Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration | journal = Immunological Reviews | volume = 230 | issue = 1 | pages = 51–74 | date = July 2009 | pmid = 19594629 | pmc = 4306344 | doi = 10.1111/j.1600-065X.2009.00792.x }}
* {{cite journal | vauthors = Sackstein R | title = The bone marrow is akin to skin: HCELL and the biology of hematopoietic stem cell homing | journal = The Journal of Investigative Dermatology | volume = 122 | issue = 5 | pages = 1061–1069 | date = May 2004 | pmid = 15140204 | doi = 10.1111/j.0022-202X.2004.09301.x | doi-access = free }}
* {{cite journal | vauthors = Konstantopoulos K, Thomas SN | title = Cancer cells in transit: the vascular interactions of tumor cells | journal = Annual Review of Biomedical Engineering | volume = 11 | pages = 177–202 | year = 2009 | pmid = 19413512 | doi = 10.1146/annurev-bioeng-061008-124949 | doi-access = free }}
* {{cite book | vauthors = Günthert U | chapter = CD44: A Multitude of Isoforms with Diverse Functions | series = Current Topics in Microbiology and Immunology | date = 1993 | title = Adhesion in Leukocyte Homing and Differentiation | volume = 184 | pages = 47–63 | pmid = 7508842 | doi = 10.1007/978-3-642-78253-4_4 | isbn = 978-3-642-78255-8 | url = http://edoc.unibas.ch/11646/1/20091115012649_4aff4ac9cb06d.pdf }}
* {{cite journal | vauthors = Yasuda M, Nakano K, Yasumoto K, Tanaka Y | title = CD44: functional relevance to inflammation and malignancy | journal = Histology and Histopathology | volume = 17 | issue = 3 | pages = 945–950 | year = 2003 | pmid = 12168806 | doi = 10.14670/HH-17.945 }}
* {{cite journal | vauthors = Sun CX, Robb VA, Gutmann DH | title = Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation | journal = Journal of Cell Science | volume = 115 | issue = Pt 21 | pages = 3991–4000 | date = November 2002 | pmid = 12356905 | doi = 10.1242/jcs.00094 | s2cid = 14243743 | doi-access =  }}
* {{cite journal | vauthors = Ponta H, Sherman L, Herrlich PA | title = CD44: from adhesion molecules to signalling regulators | journal = Nature Reviews. Molecular Cell Biology | volume = 4 | issue = 1 | pages = 33–45 | date = January 2003 | pmid = 12511867 | doi = 10.1038/nrm1004 | s2cid = 19495756 }}
* {{cite journal | vauthors = Martin TA, Harrison G, Mansel RE, Jiang WG | title = The role of the CD44/ezrin complex in cancer metastasis | journal = Critical Reviews in Oncology/Hematology | volume = 46 | issue = 2 | pages = 165–186 | date = May 2003 | pmid = 12711360 | doi = 10.1016/S1040-8428(02)00172-5 }}
{{refend}}

== External links ==
{{Commons category}}
* [https://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=indian Indian blood group system] at [[BGMUT]] Blood Group Antigen Gene Mutation Database at [[National Center for Biotechnology Information|NCBI]], [[NIH]]
* [https://web.archive.org/web/20090116012950/http://www.ihop-net.org/UniPub/iHOP/gismo/312713.html?list=0 Articles] at [[Information Hyperlinked over Proteins|IHOP]].
* {{UCSC gene info|CD44}}

{{PDB Gallery|geneid=960}}
{{Clusters of differentiation}}
{{Cell adhesion molecules}}
{{Proteoglycans}}

[[Category:Clusters of differentiation]]
[[Category:Blood antigen systems]]
[[Category:Transfusion medicine]]
[[Category:Glycoproteins]]