Adherens junction regulates cryptic lamellipodia formation for epithelial cell migration

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 form and found that they sporadically grew from around E-cadherin–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 αE-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 support c-lamellipodia formation by recruiting actin regulators, enabling epithelial cells to undergo ordered collective migration.

Caveolin‐1 influences epithelial collective cell migration via FMNL2 formin

“…We then considered the possibility that CAV1 KD reduced epithelial movement in the wound‐healing assay by affecting the ability of cells to maintain directed movement. For example, α‐catenin‐depleted cells were recently reported to close artificial wounds more slowly because they were unable to maintain directional movement into the wound [Ozawa et al., 2020]. To examine directionality, we tracked the migratory paths of individual nuclei within the monolayer and divided the total distance travelled for each cell by its calculated displacement.…”

“…Cryptic lamellipodia are veil‐like protrusions formed by cells that continue to maintain their apicobasal polarity and cell–cell contacts ([Farooqui and Fenteany, 2005; Krndija et al., 2019]). These protrusions extend beneath the cells around them and actively facilitate cell motility [Ozawa et al., 2020]. Interestingly, it has recently been reported that cryptic lamellipodia derive from dynamic actin assembly that is nucleated by Arp2/3 and WAVE focused at AJ [Ozawa et al., 2020].…”

“…These protrusions extend beneath the cells around them and actively facilitate cell motility [Ozawa et al., 2020]. Interestingly, it has recently been reported that cryptic lamellipodia derive from dynamic actin assembly that is nucleated by Arp2/3 and WAVE focused at AJ [Ozawa et al., 2020]. By stabilising F‐actin at junctions [Teo et al., 2020], FMNL2 might antagonise the nucleation of cryptic lamellipodia and thereby limit intraepithelial motility.…”

Formin homology domains of Daam1 bind to Fascin and collaboratively promote pseudopodia formation and cell migration in breast cancer

“…forces, etc. 2,3 We have demonstrated that dishevelled-associated activator of morphogenesis 1 (Daam1), a member of formin family proteins, mediates ECM-induced invadopodia extension and cell migration in breast cancer (BrCa). 4 However, the precise role of Daam1 in the assembly of actin filaments and the formation of pseudopodia is still unclear.…”

Hands and feet: Closer than you think in epithelial migration

“…This provided an opportunity for Ozawa et al to test the role of cryptic lamellipodia in epithelia migration (3). In a clever, simple experiment, they depleted cells of either p34 (an Arp2/3 component) or Nap1 (a WRC component) and mixed these with wild-type cells to generate mosaic cultures.…”