Aberrant MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation.

ABSTRACT: Little is known about the signaling network responsible for the organization of the perinuclear actin cap, a recently identified structure holding unique roles in the regulation of nuclear shape and cell directionality. In cancer cells expressing a constitutively active MET, we show a rearrangement of the actin cap filaments, which crash into perinuclear patches associated with spherical nuclei, meandering cell motility and inactivation of the mechano-transducer YAP1. MET ablation is sufficient to reactivate YAP1 and restore the cap, leading to enhanced directionality and flattened nuclei. Consistently, the introduction of a hyperactive MET in normal epithelial cells, enhances nuclear height and alters the cap organization, as also confirmed by TEM analysis. Finally, the constitutively act

SUBMITTER: Sgarzi M 

PROVIDER: S-EPMC10576810 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature