The roles of distinct Ca2+ signaling mediated by Piezo and inositol triphosphate receptor (IP3R) in the remodeling of E-cadherin during cell dissemination

Given the role of E-cadherin (E-cad) in holding epithelial cells together, the inverse relationship between E-cad levels and cell invasion has been perceived as a principle underlying the invasiveness of tumor cells. In contrast, our study employing the Drosophila model of cell dissemination demonstrates that E-cad is necessary for the invasiveness of Rasv12-transformed cells in vivo. Drosophila E-cad/{beta}-catenin disassembles at adherens junctions and assembles at invasive protrusions--the actin- and cortactin-rich invadopodia-like protrusions associated with breach of the extracellular matrix (ECM)--during cell dissemination. Loss of E-cad attenuates dissemination of Rasv12-transformed cells by impairing their ability to compromise the ECM. Strikingly, the remodeling of E-cad/{beta}-catenin subcellular distribution is controlled by two discrete intracellular calcium signaling pathways: Ca2+ release from endoplasmic reticulum via the inositol triphosphate receptor (IP3R) disassembles E-cad at adherens junctions while Ca2+ entry via the mechanosensitive channel Piezo assembles E-cad at invasive protrusions. Thus, our study provides molecular insights into the unconventional role of E-cad in cell invasion during cell dissemination in vivo and describes the discrete roles of intracellular calcium signaling in the remodeling of E-cad/{beta}-catenin subcellular localization.