Proteomics analysis of E-cadherin knockdown in epithelial breast cancer cells.

E-cadherin is the core protein of the epithelial adherens junction. Through its cytoplasmic domain, E-cadherin interacts with several signaling proteins; among them, - and -catenins mediate the linkof E-cadherin to the actin cytoskeleton. Loss of E-cadherin expression is a crucial step of epithelial-mesenchymal transition (EMT) and is involved in cancer invasion and metastatization. In human tumors,down-regulation of E-cadherin is frequently associated with poor prognosis. Despite the critical roleof E-cadherin in cancer progression, little is known about proteome alterations linked with its down-regulation. To address this point, we investigated proteomics, biophysical and functional changes ofepithelial breast cancer cell lines upon shRNA-mediated stable knockdown of E-cadherin expression(shEcad). shEcad cells showed a distinct proteomic signature including altered expression of enzymes andproteins involved in cytoskeletal dynamic and migration. Moreover, these results suggest that, besidestheir role in mechanical adhesion, loss of E-cadherin expression may contribute to cancer progressionby modifying a complex network of pathways that tightly regulate fundamental processes as oxidativestress, immune evasion and cell metabolism. Altogether, these results extend our knowledge on thecellular modifications associated with E-cadherin down-regulation in breast cancer cells.