Table 2.

CD44 Isoform Switching in Cancer

Cancer Type	Isoform Switching	Role of CD44	Reference
Ovarian cancer	CD44v to CD44s in EMT	CD44s regulates Snail and ZEB1 Isoform switch leads to mesenchymal phenotype as well as an increase in stemness and chemoresistance. TGF-β downregulates ESRP1 to induce CD44 isoform switch	[89, 95]
Lung cancer	CD44v to CD44s in EMT	ZEB1 represses ESRP1 to induce CD44 isoform switch. Isoform switch leads to increased tumorigenicity and invasiveness	[96]
Prostate cancer	CD44v to CD44s in EMT	TGF-β downregulates PCBP1 leading to CD44 isoform switch CD44s is essential for EMT and increased stemness due to TGF-β treatment	[94, 97]
Hepatocellular carcinoma	CD44v to CD44s in EMT	CD44s is essential for TGF-β-induced EMT. CD44s expression contributes to EMT and CSC characteristics Tumor initiation and stemness is regulated through c-Met/PI3K/AKT/CD44s signaling in c-Met+ HCC.	[99, 100, 139, 140]
Gallbladder cancer	CD44v9 to CD44s in EMT	Increased ZEB1 and ZEB2 downregulate ESRP1 and correlate with a CD44 isoform switch and mesenchymal phenotype. CD44s is associated with invasiveness and distant metastasis while CD44v9-positive cells are more epithelial and tumorigenic. Both CD44s and CD44v are associated with poor prognosis.	[102]
Colon cancer	CD44v9 to CD44s in EMT	Correlates with mesenchymal phenotype and poor survival.	[104]
Pancreatic cancer	CD44v to CD44s in EMT CD44s to CD44v in MET	ZEB1 represses ESRP1 to induce CD44 isoform switch. CD44s in turn promotes ZEB1 expression ZEB1 impacts CD44 isoforms, not CD44 levels. Isoform switch is associated with increased chemoresistance and CSC characteristics. CD44v associated with MET and colonization at metastatic site.	[62, 71]
Breast cancer	CD44v to CD44s in EMT CD44s to CD44v in MET	ZEB1 represses ESRP1 to induce CD44 isoform switch. CD44s in turn promotes ZEB1 expression ZEB-1 impacts CD44 isoforms, not CD44 levels. Isoform switch associated with increased chemoresistance and CSC characteristics. CD44s is associated with EMT and invasion while CD44v is associated with an epithelial phenotype and colonization at a metastatic site.	[40, 71]