Citation
S. Kuriyama, E. Theveneau, A. Benedetto, M. Parsons, M. Tanaka, G. Charras, A. Kabla and R. Mayor
Journal of Cell Biology 206:113-127 (2014)
Abstract
Abstract
Collective cell migration (CCM) and epithelial–mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell–cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell–cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like–to–fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness.
Figure sample
Inhibition of LPAR2 does not affect cell motility or chemotaxis. (A and B) Cell tracking analysis on cell clusters (A; n = 2,261 cells from four independent experiments; Student’s two-tailed t test: P = 0.25) and single cells (B; n = 1,299 cells from three independent experiments; Student’s two-tailed t test: P = 0.75). (C and D) Chemotaxis assay with controls (C) and LPAR2MO cells (D). Time projection of cell tracks color-coded according to their Chemotaxis index (from blue [0.1] to red [0.9]). (E) Chemotaxis index from experiments shown in C and D (mean chemotactic index of 22 explants from three independent experiments; Student’s two-tailed t test: P = 0.1837).
