Le Bras GF, Allison GL, Richards NF, Ansari SS, Washington MK, Andl CD. CD44 upregulation in E-cadherin-negative esophageal cancers results in cell invasion. PloS one. 6(6). e27063. PMID: 22069487 [PubMed] PMCID: PMC3206075
E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial-mesenchymal transition, CD44, upregulated in response to functional loss of E-cadherin in esophageal cell lines and cancer. Loss of E-cadherin expression correlates with increased expression of CD44 standard isoform. Using an organotypic reconstruct model, we show increased CD44 expression in areas of cell invasion is associated with MMP-9 at the leading edge. Moreover, Activin A increases cell invasion through CD44 upregulation after E-cadherin loss. Taken together, our results provide functional evidence of CD44 upregulation in esophageal cancer invasion.