Remodeling of E-cadherin subcellular localization during cell dissemination

Given the role of E-cadherin (E-cad) in holding epithelial cells together, an inverse relationship between E-cad levels and cell invasion during the epithelial-mesenchymal transi-tion and cancer metastasis has been well recognized. Here we report that E-cad is necessary for the invasiveness of RasV12-transformed intestinal epithelial cells in Drosophila. E-cad/beta- catenin disassembles at adherens junctions and assembles at invasive protrusions--the actin -and cortactin-rich invadopodium-like protrusions associated with the breach of the extracel-lular matrix (ECM)--during dissemination of RasV12-transformed intestinal epithelial cells. Loss of E-cad impairs the elongation of invasive protrusions and attenuates the ability of RasV12- transformed cells to compromise the ECM. Notably, E-cad and cortactin affect each other's localization to invasive protrusions. Given the essential roles of cortactin in cell invasion, our observations indicate that E-cad plays a role in the invasiveness of RasV12-transformed intes-tinal epithelial cells by controlling cortactin localization to invasive protrusions. Thus our study demonstrates that E-cad is a component of invasive protrusions and provides molecular in-sights into the unconventional role of E-cad in cell dissemination in vivo.