The activation of INF2 by Piezo1/Ca²⁺ is required for mesenchymal to amoeboid transition in confined environments.

ABSTRACT: To invade heterogenous tissues, transformed cells may undergo a mesenchymal to amoeboid transition (MAT). However, the molecular mechanisms regulating this transition are poorly defined. In invasive melanoma cells, we demonstrate that intracellular [Ca²⁺] increases with the degree of confinement in a Piezo1 dependent fashion. Moreover, Piezo1/Ca²⁺ is found to drive amoeboid and not mesenchymal migration in confined environments. Consistent with a model in which Piezo1 senses tension at the plasma membrane, the percentage of cells using amoeboid migration is further increased in undulating microchannels. Surprisingly, amoeboid migration was not promoted by myosin light chain kinase (MLCK), which is sensitive to intracellular [Ca²⁺]. Instead, we report that P

SUBMITTER: Kar N 

PROVIDER: S-EPMC10515767 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature