Aberrant MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
14 10 2023
14 10 2023
Historique:
received:
17
12
2022
accepted:
03
10
2023
medline:
23
10
2023
pubmed:
15
10
2023
entrez:
14
10
2023
Statut:
epublish
Résumé
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 active YAP1 mutant YAP5SA is able to overcome the effects of oncogenic MET. Overall, our work describes a signaling axis empowering MET-mediated YAP1 dampening and actin cap misalignment, with implications for nuclear shape and cell motility.
Identifiants
pubmed: 37838732
doi: 10.1038/s42003-023-05411-y
pii: 10.1038/s42003-023-05411-y
pmc: PMC10576810
doi:
Substances chimiques
Actins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1044Informations de copyright
© 2023. Springer Nature Limited.
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