title: Glioblastoma motility occurs in the absence of actin polymer.
abstract: 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.
authors.affiliation: Tumor Development Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Panopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.forename: Rati
authors.initials: R
authors.lastname: Fotedar
authors.forename: Robert L
authors.initials: RL
authors.lastname: Margolis
mesh_terms: D000199:Actins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D058105:Polymerization; D011554:Pseudopodia / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins