Dasatinib suppresses collective cell migration through the coordination of focal adhesion and E-cadherin in colon cancer cells

Abstract

Collective cell migration is an important process in cancer metastasis. Unlike single-cell migration, collective cell migration requires E-cadherin expression in the cell cohort. However, the mechanisms underlying cellular contact and focal adhesions remain unclear. In this study, Src was hypothesized to coordinate focal adhesion and Rab11-mediated E-cadherin distribution during collective cell migration. This study primarily used confocal microscopy to visualize the 3D structure of cell-cell contacts with associated molecules. These results demonstrate that the clinical Src inhibitor dasatinib was less toxic to HT-29 colon cancer cells; instead, the cells aggregated. 3D immunofluorescence imaging showed that Rab11 was localized with E-cadherin at the adherens junctions of the apical cell-cell contacts. In the transwell assay, Rab11 colocalized with a broad range of E-cadherin proteins in collectively migrated cells, and dasatinib treatment significantly suppressed collective cell migration. Transmission electron microscopy demonstrated that dasatinib treatment increased cell membrane protrusion contacts and generated spaces between cells, which may allow epidermal growth factor receptor activity at the cell-cell contacts. This study suggests that dasatinib treatment does not inhibit cell survival but targets Src at different cellular compartments in the coordination of focal adhesions and cell-cell contacts in collective cell migration through E-cadherin dynamics in colon cancer cells.