Glioblastoma motility occurs in the absence of actin polymer
| Autor: | Andreas Panopoulos, Michael Howell, Robert L. Margolis, Rati Fotedar |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
rac1 GTP-Binding Protein
rho GTP-Binding Proteins Arp2/3 complex Motility RAC1 macromolecular substances Microtubules Polymerization 03 medical and health sciences Actin remodeling of neurons 0302 clinical medicine Microtubule Cell Movement Tumor Cells Cultured Humans Actin-binding protein Pseudopodia Molecular Biology Actin 030304 developmental biology 0303 health sciences biology Cell Biology Articles Fibroblasts Actins Cell biology Cell Motility Mutation biology.protein Glioblastoma 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | Human glioblastoma cells are motile in the absence of intact actin polymers, following suppression of actin assembly by specific inhibitors. On the other hand, suppression of microtubules completely blocks motility. These results are clearly divergent from the standard model of actin-based cell motility in mammalian cells. In fibroblasts and keratocytes, motility is actin dependent, while microtubules play a secondary role, providing directional guidance. We demonstrate here that the motility of glioblastoma cells is exceptional, in that it occurs in cells depleted of assembled actin. Cells display persistent motility in the presence of actin inhibitors at concentrations sufficient to fully disassemble actin. Such actin independent motility is characterized by the extension of cell protrusions containing abundant microtubule polymers. Strikingly, glioblastoma cells exhibit no motility in the presence of microtubule inhibitors, at concentrations that disassemble labile microtubule polymers. In accord with an unconventional mode of motility, glioblastoma cells have some unusual requirements for the Rho GTPases. While Rac1 is required for lamellipodial protrusions in fibroblasts, expression of dominant negative Rac1 does not suppress glioblastoma migration. Other GTPase mutants are largely without unique effect, except dominant positive Rac1-Q61L, and rapidly cycling Rac1-F28L, which substantially suppress glioblastoma motility. We conclude that glioblastoma cells display an unprecedented mode of intrinsic motility that can occur in the absence of actin polymer, and that appears to require polymerized microtubules. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|