Description
CD44 is a single-pass type I transmembrane protein and functions as a cellular adhesion molecule for hyaluronic acid, a major component of the extracellular matrix. It exists in numerous isoforms that are generated through alternative splicing of CD44 precursor mRNA. Whereas the standard isoform of CD44 (CD44s) is expressed predominantly in hematopoietic cells and normal epithelial cell subsets, CD44v (variant) isoforms, which contain additional insertions in the membrane-proximal extracellular region, are highly expressed in epithelial-type carcinomas. Moreover, CD44 is reported to be a cell surface marker for cancer stem cells (CSCs) derived from solid tumors including breast, prostate, colon, head and neck and pancreatic cancer. Expression of CD44, especially variant isoforms (CD44 v8-10), contributes to reactive oxygen species (ROS) defense through upregulation of the synthesis of reduced glutathione (GSH), the primary intracellular antioxidant. CD44 v8-10 interacts with and stabilizes xCT, a subunit of the cystine-glutamate transporter xc(-), and thereby promotes cystine uptake for GSH synthesis. The ability to avoid the consequences of exposure to high levels of ROS is required for cancer cell survival and propagation in vivo. CSCs (whose defense against ROS is enhanced by CD44v8-10) are thus thought to drive tumor growth, chemoresistance and metastasis.
