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

Dev Cell. 2021 Oct 25;56(20):2841-2855.e8. doi: 10.1016/j.devcel.2021.09.007. Epub 2021 Sep 23.

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.

Keywords: adhesion; cancer; grids; laminin; microfabrication; microtubule; migration; stiffness; traction force; tumorsphere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Fetal Proteins / metabolism
  • Formins / metabolism*
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Microfilament Proteins / metabolism
  • Neoplasm Invasiveness / pathology*

Substances

  • Fetal Proteins
  • Formins
  • Microfilament Proteins