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Torrino S, Grasset EM, Audebert S, et al. Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis. Cell Metab. 2021;33(7):1342-1357.e10doi: 10.1016/j.cmet.2021.05.009.
Torrino, S., Grasset, E. M., Audebert, S., Belhadj, I., Lacoux, C., Haynes, M., Pisano, S., Abélanet, S., Brau, F., Chan, S. Y., Mari, B., Oldham, W. M., Ewald, A. J., & Bertero, T. (2021). Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis. Cell metabolism, 33(7), 1342-1357.e10. https://doi.org/10.1016/j.cmet.2021.05.009
Torrino, Stéphanie, et al. "Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis." Cell metabolism vol. 33,7 (2021): 1342-1357.e10. doi: https://doi.org/10.1016/j.cmet.2021.05.009
Torrino S, Grasset EM, Audebert S, Belhadj I, Lacoux C, Haynes M, Pisano S, Abélanet S, Brau F, Chan SY, Mari B, Oldham WM, Ewald AJ, Bertero T. Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis. Cell Metab. 2021 Jul 06;33(7):1342-1357.e10. doi: 10.1016/j.cmet.2021.05.009. Epub 2021 Jun 07. PMID: 34102109.
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Cell Metab. 2021 Jul 06;33(7):1342-1357.e10. doi: 10.1016/j.cmet.2021.05.009. Epub 2021 Jun 07.

Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis.

Cell metabolism

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

Affiliations

  1. Université Côte d'Azur, CNRS, IPMC, Valbonne, France. Electronic address: [email protected].
  2. Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  3. Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.
  4. Université Côte d'Azur, CNRS, IPMC, Valbonne, France.
  5. Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France.
  6. Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  7. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  8. Université Côte d'Azur, CNRS, IPMC, Valbonne, France. Electronic address: [email protected].

PMID: 34102109 DOI: 10.1016/j.cmet.2021.05.009

Abstract

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.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: breast cancer; cancer cell metabolism; glutamine metabolism; glutamylation; mechanobiology; microtubules; posttranslational modifications

Conflict of interest statement

Declaration of interests S.Y.C. has served as a consultant for Zogenix, Aerpio, and United Therapeutics; S.Y.C. holds research grants from Actelion and Pfizer. S.Y.C. and T.B. have filed patent applic

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Grant support