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PTEN inhibits AMPK to control collective migration

Author

Listed:
  • Florent Peglion

    (Institut Pasteur, CNRS UMR3691, Université Paris Cité, Équipe Labellisée Ligue Contre le Cancer)

  • Lavinia Capuana

    (Institut Pasteur, CNRS UMR3691, Université Paris Cité, Équipe Labellisée Ligue Contre le Cancer
    Sorbonne Université)

  • Isabelle Perfettini

    (Institut Pasteur, CNRS UMR3691, Université Paris Cité, Équipe Labellisée Ligue Contre le Cancer)

  • Laurent Boucontet

    (Institut Pasteur, CNRS UMR3738)

  • Ben Braithwaite

    (Institut Pasteur, CNRS UMR3691, Université Paris Cité, Équipe Labellisée Ligue Contre le Cancer)

  • Emma Colucci-Guyon

    (Institut Pasteur, CNRS UMR3738)

  • Emie Quissac

    (Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC University Paris 04 UMR S1127, Institut du Cerveau, ICM)

  • Karin Forsberg-Nilsson

    (Uppsala University)

  • Flora Llense

    (Institut Pasteur, CNRS UMR3691, Université Paris Cité, Équipe Labellisée Ligue Contre le Cancer
    Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR7622)

  • Sandrine Etienne-Manneville

    (Institut Pasteur, CNRS UMR3691, Université Paris Cité, Équipe Labellisée Ligue Contre le Cancer)

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.

Suggested Citation

  • Florent Peglion & Lavinia Capuana & Isabelle Perfettini & Laurent Boucontet & Ben Braithwaite & Emma Colucci-Guyon & Emie Quissac & Karin Forsberg-Nilsson & Flora Llense & Sandrine Etienne-Manneville, 2022. "PTEN inhibits AMPK to control collective migration," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31842-y
    DOI: 10.1038/s41467-022-31842-y
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    1. Jun Hee Lee & Hyongjong Koh & Myungjin Kim & Yongsung Kim & Soo Young Lee & Roger E. Karess & Sang-Hee Lee & Minho Shong & Jin-Man Kim & Jaeseob Kim & Jongkyeong Chung, 2007. "Energy-dependent regulation of cell structure by AMP-activated protein kinase," Nature, Nature, vol. 447(7147), pages 1017-1020, June.
    2. Matthias Osswald & Erik Jung & Felix Sahm & Gergely Solecki & Varun Venkataramani & Jonas Blaes & Sophie Weil & Heinz Horstmann & Benedikt Wiestler & Mustafa Syed & Lulu Huang & Miriam Ratliff & Kianu, 2015. "Brain tumour cells interconnect to a functional and resistant network," Nature, Nature, vol. 528(7580), pages 93-98, December.
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