CD44 variant 6 isoform (CD44v6)

CD44 variant 6 isoform (CD44v6) is a type 1 transmembrane glycoprotein and a splice variant of the CD44 receptor, produced by alternative splicing of the CD44 gene mRNA to include exon v6. CD44v6 is distinguished by its extracellular v6-encoded domain, which confers unique functional properties distinct from the standard isoform (CD44s). CD44v6 participates in cell adhesion, migration, and signal transduction by acting as a co-receptor for ligands such as hyaluronic acid, osteopontin, and various growth factors. Notably, CD44v6 is implicated in regulating key pathways for cell proliferation, survival, apoptosis resistance, and autophagy, contributing to tumor progression, metastasis, and chemoresistance in several cancers. CD44v6 can promote resistance to cell death by physically interfering with the FAS apoptotic pathway and by acting as a necessary co-receptor for receptor tyrosine kinases like c-Met and VEGFR-2, amplifying growth and survival signaling in tumor cells. Its expression is upregulated in many cancers and correlates with more aggressive disease, making it a promising therapeutic target and clinical biomarker, albeit with concerns about on-target toxicity due to low-level expression in normal tissues[1][2][3][4][5][6].

Other names

CD44v6CD44 exon v6-containing isoformCD44 variant exon 6 isoform

Antibody blockade of CD44v6 prevents its interaction with partners and impairs its function as a co-receptor, thereby reducing tumor cell survival, migration, and invasiveness[6]. - Inhibition of CD44v6-mediated chemoresistance and apoptosis evasion (e.g., through FAS pathway modulation)[4]. - Interference with growth factor presentation (e.g., hepatocyte growth factor [HGF] and c-Met activation), which can disrupt tumor signaling pathways[6].