Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis

Stéphanie Torrino, Eloise M. Grasset, Stephane Audebert, Ilyes Belhadj, Caroline Lacoux, Meagan Haynes, Sabrina Pisano, Sophie Abélanet, Frederic Brau, Stephen Y. Chan, Bernard Mari, William M. Oldham, Andrew J. Ewald, Thomas Bertero

Research output: Contribution to journalArticlepeer-review


Mechanical signals from the tumor microenvironment modulate cell mechanics and influence cell metabolism to promote cancer aggressiveness. Cells withstand external forces by adjusting the stiffness of their cytoskeleton. Microtubules (MTs) act as compression-bearing elements. Yet how cancer cells regulate MT dynamic in response to the locally constrained environment has remained unclear. Using breast cancer as a model of a disease in which mechanical signaling promotes disease progression, we show that matrix stiffening rewires glutamine metabolism to promote MT glutamylation and force MT stabilization, thereby promoting cell invasion. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, decreased MT glutamylation by overexpressing tubulin mutants lacking glutamylation site(s) decreased MT stability, thereby hampering cancer aggressiveness in vitro and in vivo. Together, our results decipher part of the enigmatic tubulin code that coordinates the fine-tunable properties of MT and link cell metabolism to MT dynamics and cancer aggressiveness.

Original languageEnglish (US)
Pages (from-to)1342-1357.e10
JournalCell Metabolism
Issue number7
StatePublished - Jul 6 2021


  • breast cancer
  • cancer cell metabolism
  • glutamine metabolism
  • glutamylation
  • mechanobiology
  • microtubules
  • posttranslational modifications

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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