Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion

Pascale Monzo, Michele Crestani, Yuk Kien Chong, Andrea Ghisleni, Katharina Hennig, Qingsen Li, Nikolaos Kakogiannos, Monica Giannotta, Cristina Richichi, Tania Dini, Elisabetta Dejana, Paolo Maiuri, Martial Balland, Michael P. Sheetz, Giuliana Pelicci, Beng Ti Ang, Carol Tang, Nils C. Gauthier

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Glioblastoma are heterogeneous tumors composed of highly invasive and highly proliferative clones. Heterogeneity in invasiveness could emerge from discrete biophysical properties linked to specific molecular expression. We identified clones of patient-derived glioma propagating cells that were either highly proliferative or highly invasive and compared their cellular architecture, migratory, and biophysical properties. We discovered that invasiveness was linked to cellular fitness. The most invasive cells were stiffer, developed higher mechanical forces on the substrate, and moved stochastically. The mechano-chemical-induced expression of the formin FMN1 conferred invasive strength that was confirmed in patient samples. Moreover, FMN1 expression was also linked to motility in other cancer and normal cell lines, and its ectopic expression increased fitness parameters. Mechanistically, FMN1 acts from the microtubule lattice and promotes a robust mechanical cohesion, leading to highly invasive motility.

Original languageEnglish (US)
Pages (from-to)2841-2855
Number of pages15
JournalDevelopmental cell
Volume56
Issue number20
DOIs
StatePublished - Oct 25 2021

Keywords

  • adhesion
  • cancer
  • grids
  • laminin
  • microfabrication
  • microtubule
  • migration
  • stiffness
  • traction force
  • tumorsphere

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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