PTEN Inhibits AMPK to Control Collective Migration

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 11

PMID 35953476

Authors

Florent Peglion

Lavinia Capuana

Isabelle Perfettini

Laurent Boucontet

Ben Braithwaite

Emma Colucci-Guyon

Emie Quissac

Karin Forsberg-Nilsson

Flora Llense

Sandrine Etienne-Manneville

Affiliations

Soon will be listed here.

Abstract

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.

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