Year: 2022
Type: article
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.
Source: Nature Communications
Institutions: Centre National de la Recherche Scientifique, Institut Pasteur, Université Paris Cité, Biologie cellulaire physiologique et pathologique, Sorbonne Université, Biologie du Développement et Cellules Souches, Inserm, Institut du Cerveau, Université Pierre-et-Marie-Curie, Uppsala University, Science for Life Laboratory, Laboratoire de Biologie du Développement, Institut de Biologie Paris-Seine, La Ligue Contre le Cancer
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,328
OpenAlex ID: W4291004591