Several signaling molecules have been reported to control E-cadherin expression. Kleinberg et al. [25] have found that the epithelial–mesenchymal transition and E-cadherin expression are influenced by several growth factors that are responsive to signaling, as well as by a variety of polypeptide growth pathways. Loss of E-cadherin has wide-ranging transcriptional and functional consequences for human breast epithelial cells. Loss of E-cadherin is sufficient to confer metastatic ability on breast cancer
tsa inhibitor that are otherwise essentially nonmetastatic. Using a dominant-negative E-cadherin mutant, Onder and colleagues [23] have determined that the acquisition of metastatic ability by cancer cells after E-cadherin loss is not attributable solely to disruption of intercellular adhesion contacts. Instead, it is the additional loss of E-cadherin protein that activates an epithelial–mesenchymal transition, attained by increased cellular motility, invasiveness, and resistance to apoptosis. This study also suggests that point mutations in the extracellular domain that preserve the cytoplasmic tail of E-cadherin are not likely to result in an epithelial–mesenchymal transition (EMT) or to afford functional traits that allow completion of the later steps of metastasis. In contrast, complete elimination of E-cadherin
expression via truncation mutation or locus repression or loss results in the activation of malignancy-associated traits [26]. Thus, loss of E-cadherin, in combination with certain additional oncogenic lesions, results in the acquisition of multiple functional traits that contribute to the completion of several rate-limiting steps in the invasion-metastasis cascade.
