Adherens junction serves to generate cryptic lamellipodia required for collective migration of epithelial cells

Abstract

Collective migration of epithelial cells plays crucial roles in various biological processes such as cancer invasion. In migrating epithelial sheets, leader cells form lamellipodia to advance, and follower cells also form similar motile apparatus at cell-cell boundaries, which are called cryptic lamellipodia (c-lamellipodia). Using adenocarcinoma-derived epithelial cells, we investigated how c-lamellipodia are generated, and found that they sporadically grew from Ecadherin-based adherens junctions (AJs). WAVE and Arp2/3 complexes were localized along the AJs, and silencing them not only interfered with c-lamellipodia formation but also prevented follower cells from trailing the leaders. Disruption of AJs by removing aE-catenin resulted in uncontrolled c-lamellipodia growth, and this was brought about by myosin II activation and the resultant contraction of AJ-associated actomyosin cables. Additional observations indicated that c-lamellipodia tended to grow at mechanically weak sites of the junction. We conclude that AJs not only tie cells together but also generate c-lamellipodia by recruiting actin regulators, enabling epithelial cells to undergo ordered collective migration.

Symmetry Breaking and Epithelial Cell Extrusion

“…It has been suggested that cortical contractility may operate for single cells, whereas lamellipodia may be involved where larger cells, or small groups of cells, are being extruded [ 29 ]. These mechanisms are not necessarily exclusive, as cryptic lamellipodia which extend underneath migrating epithelial cells can also form AJ [ 36 , 37 ].…”

Digital Spindle: A New Way to Explore Mitotic Functions by Whole Cell Data Collection and a Computational Approach

“…Scale bars: 1 µm. (c) Comparison of optical sectioned images of human colon carcinoma (Caco2) cells expressing Lifeact-red fluorescent protein (RFP) visualizing actin filaments [21], collected by wide-field, TIRF microscopy (TIRFM), and lattice light-sheet microscopy (LLSM) (left column). In wide-field and TIRFM, the same field of view was imaged using a TIRFM system (Nikon).…”