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
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

1044

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Michela Sgarzi (M)

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Martina Mazzeschi (M)

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Spartaco Santi (S)

Institute of Molecular Genetics, National Research Council of Italy, Bologna, Italy.
IRCCS-Institute Orthopaedic Rizzoli, Bologna, Italy.

Elisa Montacci (E)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Tito Panciera (T)

Department of Molecular Medicine, University of Padua, Padua, Italy.

Enea Ferlizza (E)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Cinzia Girone (C)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Alessandra Morselli (A)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Valerio Gelfo (V)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Rikke Sofie Kuhre (RS)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Carola Cavallo (C)

Laboratory of Preclinical Studies for Regenerative Medicine of the Musculoskeletal System (RAMSES), (IRCCS) Istituto Ortopedico Rizzoli, Bologna, Italy.

Sabrina Valente (S)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Gianandrea Pasquinelli (G)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Balazs Győrffy (B)

Semmelweis University Dept. of Bioinformatics and 2nd Dept. Of Pediatrics, Budapest, Hungary.
TTK Cancer Biomarker Research Group, Institute of Enzymology, Budapest, Hungary.

Gabriele D'Uva (G)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Donatella Romaniello (D)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy. donatella.romaniello@unibo.it.

Mattia Lauriola (M)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy. mattia.lauriola2@unibo.it.
Centre for Applied Biomedical Research (CRBA), Bologna University Hospital Authority St. Orsola -Malpighi Polyclinic, Bologna, Italy. mattia.lauriola2@unibo.it.

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