Department of Surgery, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One. 2011;6(11):e27063. doi: 10.1371/journal.pone.0027063. Epub 2011 Nov 1.
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.
E-钙黏蛋白在上皮-间充质转化和上皮肿瘤发生过程中经常丢失。我们发现 CD44 在食管细胞系和癌症中对 E-钙黏蛋白功能丧失的反应上调，是上皮-间充质转化的一个标志物。E-钙黏蛋白表达的丧失与 CD44 标准同工型表达的增加相关。通过器官型重建模型，我们发现细胞侵袭区域的 CD44 表达增加与 MMP-9 在前沿的表达相关。此外，在 E-钙黏蛋白丢失后，激活素 A 通过 CD44 的上调增加细胞侵袭。总之，我们的结果提供了 CD44 在食管癌细胞侵袭中上调的功能证据。
