Tumor Development Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Mol Biol Cell. 2011 Jul 1;22(13):2212-20. doi: 10.1091/mbc.E10-10-0849. Epub 2011 May 5.
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.
在成纤维细胞和成角膜细胞中，运动依赖于肌动蛋白，而微管则起次要作用，提供定向指导。我们在这里证明，神经胶质瘤细胞的运动是特殊的，因为它发生在组装的肌动蛋白耗尽的细胞中。在足以完全解聚肌动蛋白的浓度的肌动蛋白抑制剂存在下，细胞表现出持续的运动。这种不依赖肌动蛋白的运动的特征是含有丰富的微管聚合物的细胞突起的延伸。引人注目的是，在足以解聚不稳定微管聚合物的浓度下，神经胶质瘤细胞在微管抑制剂存在下没有运动。与非常规的运动模式一致，神经胶质瘤细胞对 Rho GTPases 有一些不寻常的要求。虽然 Rac1 对于成纤维细胞中的片状伪足突起是必需的，但表达显性负 Rac1 并不能抑制神经胶质瘤的迁移。其他 GTPase 突变体基本上没有独特的作用，除了快速循环的 Rac1-F28L，它大大抑制了神经胶质瘤的运动。我们得出结论，神经胶质瘤细胞表现出一种前所未有的内在运动模式，这种模式可以在没有肌动蛋白聚合物的情况下发生，并且似乎需要聚合的微管。
