CD44 gene

CD44 is a protein coding gene located on chromosome 11p13. The protein encoded by this gene is a receptor for hyaluronic acid (HA). It is a cell surface glycoprotein(CD44) involved in cell-cell interactions, cell adhesion and migration to sense and respond to changes in the tissue microenvironment (Yoshida T et al. 2012). Transcripts of this gene undergo a complex alternative splicing process that results in many functionally distinct isoforms. The nature of some of these full-length variants is unknown. Alternative splicing is the basis for the structural and functional diversity of this protein and may be related to tumor metastasis.

CD 44, as a hyaluronic acid receptor, can also interact with other ligands such as collagens and matrix metalloproteinases (MMPs). CD44 is involved in a variety of cellular functions, including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis.

The encoded protein is involved in a variety of cellular functions, including T lymphocyte activation, circulation and homing, hematopoiesis, inflammation, and response to bacterial infection (Funaro A et al. 1994). It binds extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases via its ectodomain and serves as a platform for signal transduction by assembling protein complexes containing receptor kinases and membrane proteases via its cytoplasmic domain (Midgley AC et al. 2013). These effectors include PKN2 (protein kinase), the RhoGTPases RAC1 and RHOA, Rho kinase (ROCK1+ 2), and phospholipase C. They coordinate signaling pathways that promote calcium mobilization and actin-mediated reorganization of the cytoskeleton, which are important for cell migration and adhesion (Bourguignon LY et al. 2004).

Diseases associated with CD44 include:

• Lichen sclerosus (Kaya G et al. 2000)

and

• Pleural mesothelioma.

1. Bourguignon LY et al (2004) Hyaluronan-CD44 interaction with Rac1-dependent protein kinase N-gamma promotes phospholipase Cgamma1 activation, Ca(2+) signaling, and cortactin-cytoskeleton function leading to keratinocyte adhesion and differentiation. J Biol Chem 279:29654-29669.
2. Funaro A et al (1994) Stimulation of T cells via CD44 requires leukocyte-function-associated antigen interactions and interleukin-2 production. Hum Immunol 40:267-278.
3. Kaya G et al (2000) Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus. J Invest Dermatol. 2000 Dec;115(6):1054-8.
4. Midgley AC et al. (2013) 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. J Biol Chem 288:14824-1438.
5. Yoshida T et al (2012) CD44 in human glioma correlates with histopathological grade and cell migration. Pathol Int 62:463-470.