CD44 antigen variant 9 (CD44v9)

CD44 antigen variant 9 (CD44v9) is a specific isoform of the CD44 cell surface adhesion receptor, generated by alternative splicing to include variant exon 9. CD44v9, like other CD44 variants, has distinct biological properties from the standard form (CD44s), and is frequently upregulated in cancer stem-like cells, particularly in solid tumors such as gastric and colorectal cancer[6]. It plays critical roles in regulating cell adhesion, migration, proliferation, resistance to cell death (notably by modulating apoptosis and ferroptosis), and tissue regeneration[2][4][6]. Mechanistically, CD44v9-containing isoforms interact with and stabilize the cystine-glutamate transporter xCT, supporting glutathione synthesis and cellular defense against oxidative stress, which contributes to chemoresistance in cancer cells[2]. Expression of CD44v9 is associated with poor prognosis and increased chemoresistance in some cancers, and it serves as a functional and prognostic cell surface marker for certain cancer stem cell populations, as well as a marker for regenerating/metaplastic epithelium during gastrointestinal tissue repair[4][6]. Antibodies against CD44v9 and inhibitors targeting the xCT pathway represent experimental therapeutic strategies, though their clinical translation faces challenges due to the molecule's broad tissue distribution and physiological roles[2][4][6].

Other names

CD44 variant isoform 9CD44v9CD44 variant 9

Blocking CD44v9 inhibits its role in maintaining cancer cell resistance to apoptosis/ferroptosis by disrupting xCT stabilization and glutathione synthesis[2] Antibody-mediated binding may mark or modulate cancer stem cell populations[6]