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Updated: Jul 29, 2025

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell

Eva Crosas-Molist1,2, Vittoria Graziani1,2, Oscar Maiques1,2

  • 1Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK.

Nature Communications
|May 22, 2023
PubMed

Insights

AMP-activated protein kinase (AMPK) acts as an adhesion sensor, controlling cancer cell migration. It links cell energetics and the cytoskeleton, influencing mitochondrial dynamics and cell movement crucial for cancer dissemination.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Metabolic Regulation

Background:

  • Cell migration is a fundamental process in cancer dissemination and metastasis.
  • Understanding the molecular mechanisms that regulate cell migration is critical for developing anti-cancer therapies.

Purpose of the Study:

  • To investigate the role of AMP-activated protein kinase (AMPK) in controlling cancer cell migration.
  • To elucidate how AMPK functions as an adhesion-sensing molecular hub linking cell energetics and cytoskeletal dynamics.

Main Methods:

  • Utilized 3D matrix models to study cancer cell migration.
  • Analyzed the impact of AMPK activation on mitochondrial dynamics and cytoskeletal remodeling.
  • Investigated the effects of modulating adhesion, mitochondrial fusion, and AMPK activity on cell migration.
  • Assessed AMPK inhibition in vivo for metastatic potential and examined human tumors for AMPK-driven switches.

Main Results:

  • AMPK activation in low-adhesion, fast-migrating amoeboid cancer cells is linked to low ATP/AMP ratios.
  • AMPK induces mitochondrial fission, reducing oxidative phosphorylation and ATP production.
  • AMPK inactivates Myosin Phosphatase, promoting Myosin II-dependent amoeboid migration.
  • Reduced adhesion, mitochondrial fusion, or AMPK activation promotes rounded-amoeboid migration.

Conclusions:

  • AMPK acts as a mechano-metabolic sensor, linking cellular energetics to cytoskeletal regulation.
  • Mitochondrial dynamics are critical regulators of cell migration.
  • AMPK inhibition suppresses the metastatic potential of amoeboid cancer cells.
  • An AMPK/mitochondrial-driven switch is observed in disseminating cancer cells within human tumors.

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