CD44 variant 9 (CD44v9)

CD44 variant 9 (CD44v9) is a cell surface transmembrane glycoprotein and a splice variant of the CD44 family, generated by the inclusion of exon v9 in its extracellular domain[1][4][5]. It functions as an adhesion receptor, contributing to cellular aggregation, migration, and tumor invasion by binding extracellular matrix components (including hyaluronan, osteopontin, and collagen)[1][5]. CD44v9 distinguishes itself from other CD44 isoforms by its ability to interact with and stabilize the cystine/glutamate transporter (xCT/SLC7A11), which raises intracellular glutathione levels and enhances tumor cell resistance to oxidative stress and therapy-induced ferroptosis[1][6]. High CD44v9 expression marks cancer stem cell populations, correlates with poor prognosis, promotes tumor progression, and contributes to chemoresistance, recurrence, and metastasis in various epithelial cancers[2][6]. CD44v9 is widely studied as a prognostic and basal subtype biomarker in cancers of the stomach, bladder, and colon, among others[2][6]. Key points: - **CD44 variant 9 is a cell surface receptor** formed via alternative splicing of the CD44 gene, involving variant exon 9[4][5]. - **It is a widely validated therapeutic and prognostic target in oncology**, especially for aggressive and stem-like tumor subtypes[2][6]. - **No drugs are approved to specifically target CD44v9**, but inhibitors of the CD44v9–xCT axis (such as sulfasalazine targeting xCT) are being explored for cancer treatment[6]. - **Expression of CD44v9 is clinically significant** for cancer stemness, therapy resistance, and outcome prediction in several tumor types[2][6].

Other names

CD44v9CD44 variant exon 9CD44 isoform v9

Drugs that disrupt the CD44v9–xCT interaction can impair cystine uptake, deplete glutathione, elevate oxidative stress, and induce cancer cell death by ferroptosis[6][1].