Tuning Collective Cell Migration by Cell–Cell Junction Regulation

Abstract

Collective cell migration critically depends on cell -cell interactions coupled to a dynamic actin cytoskeleton. Important cell-cell adhesion receptor systems implicated in controlling collective movements include cadherins, immunoglobulin superfamily members (L1CAM, NCAM, ALCAM), Ephrin/Eph receptors, Slit/Robo, connexins and integrins, and an adaptive array of intracellular adapter and signaling proteins. Depending on molecular composition and signaling context, cell -cell junctions adapt their shape and stability, and this gradual junction plasticity enables different types of collective cell movements such as epithelial sheet and cluster migration, branching morphogenesis and sprouting, collective network migration, as well as coordinated individual-cell migration and streaming. Thereby, plasticity of cell -cell junction composition and turnover defines the type of collective movements in epithelial, mesenchymal, neuronal, and immune cells, and defines migration coordination, anchorage, and cell dissociation. We here review cell -cell adhesion systems and their functions in different types of collective cell migration as key regulators of collective plasticity.

Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization

“…However, it remains unclear how proteins involved in collective migration differ from those involved in single cell migration. One attractive model for collective migration argued the importance of supracellular cytoskeletal organization, where the dynamics of the cytoskeleton is shared between multiple cells to jointly generate force for migration and polarization . Our finding that Girdin is involved in actin remodeling at the cell‐cell interface in A431 cancer cell groups (Figure C) supports the model, but it is unknown at present whether it was a direct or indirect effect of Girdin depletion.…”

Cranial Neural Crest Explants

“…The Use of the CNC explant assay (Alfandari et al 2003) has led to many discoveries, including the findings that CNC cells use fibronectin and integrin α5β1 to migrate, and that they perform the majority of their migration by keeping cell–cell contact, a phenomenon called collective cell migration (Carmona-Fontaine et al 2008; Friedl and Mayor 2017). Today, this assay is used to investigate the basic cellular and molecular mechanisms of CNC migration and of collective migration in general (Friedl and Mayor 2017).…”

“…Today, this assay is used to investigate the basic cellular and molecular mechanisms of CNC migration and of collective migration in general (Friedl and Mayor 2017). While an incredibly powerful system, experimenters should be aware that it may not always be useful for studying the functions of certain genes during CNC migration.…”

“…By varying the size of these openings, one can test the ability of the CNC to squeeze through openings and therefore challenge the fluidity of the explant (Cousin et al 2012). The concept of fluidity of tissues undergoing collective cell migration is important, and CNC cells are one of the few models that allow it to be tested and quantified (Friedl and Mayor 2017). …”

The Na+/H+ exchanger NHE1 localizes as clusters to cryptic lamellipodia and accelerates collective epithelial cell migration

“…In addition, collective cell migration plays central roles in diseases such as cancer and fibrosis (Haeger et al . ; Mayor & Etienne‐Manneville, ; Friedl & Mayor, ; Khalil et al . ).…”