PTEN inhibits AMPK to control collective migration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 08 2022
11 08 2022
Historique:
received:
15
09
2021
accepted:
05
07
2022
entrez:
11
8
2022
pubmed:
12
8
2022
medline:
16
8
2022
Statut:
epublish
Résumé
Pten is one of the most frequently mutated tumour suppressor gene in cancer. PTEN is generally altered in invasive cancers such as glioblastomas, but its function in collective cell migration and invasion is not fully characterised. Herein, we report that the loss of PTEN increases cell speed during collective migration of non-tumourous cells both in vitro and in vivo. We further show that loss of PTEN promotes LKB1-dependent phosphorylation and activation of the major metabolic regulator AMPK. In turn AMPK increases VASP phosphorylation, reduces VASP localisation at cell-cell junctions and decreases the interjunctional transverse actin arcs at the leading front, provoking a weakening of cell-cell contacts and increasing migration speed. Targeting AMPK activity not only slows down PTEN-depleted cells, it also limits PTEN-null glioblastoma cell invasion, opening new opportunities to treat glioblastoma lethal invasiveness.
Identifiants
pubmed: 35953476
doi: 10.1038/s41467-022-31842-y
pii: 10.1038/s41467-022-31842-y
pmc: PMC9372137
doi:
Substances chimiques
AMP-Activated Protein Kinases
EC 2.7.11.31
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4528Informations de copyright
© 2022. The Author(s).
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