Morimura Shigeru, Takahashi Kazuhide
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, Yokohama 241-0815, Japan.
Int J Cell Biol. 2011;2011:615912. doi: 10.1155/2011/615912. Epub 2011 Sep 25.
Cell migration is considered necessary for the invasion that accompanies the directional formation of the cellular protrusions termed lamellipodia. In invasive breast cancer MDA-MB-231 cells, lamellipodia formation is preceded by translocation of the actin cytoskeletal regulatory protein WAVE2 to the leading edge. WAVE2 translocation and lamellipodia formation require many signaling molecules, including PI3K, Rac1, Pak1, IRSp53, stathmin, and EB1, but whether these molecules are necessary for invasion remains unclear. In noninvasive breast cancer MCF7 cells, no lamellipodia were induced by IGF-I, whereas in MDA-MB-231 cells, Rac1, stathmin, and EB1 were overexpressed. Depletion of Rac1 or stathmin by small interfering RNA abrogated the IGF-I-induced invasion of MDA-MB-231 cells; however, depletion of EB1 did not, indicating the necessity of Rac1 and stathmin but not EB1 for invasion. The signaling pathway leading to cell invasion may not be identical but shares some common molecules, leading to cell migration through lamellipodia formation.
细胞迁移被认为是伴随称为片状伪足的细胞突起定向形成的侵袭所必需的。在侵袭性乳腺癌MDA - MB - 231细胞中，片状伪足形成之前，肌动蛋白细胞骨架调节蛋白WAVE2会转位至前沿。WAVE2转位和片状伪足形成需要许多信号分子，包括PI3K、Rac1、Pak1、IRSp53、stathmin和EB1，但这些分子对于侵袭是否必要仍不清楚。在非侵袭性乳腺癌MCF-7细胞中，IGF-I不会诱导片状伪足形成，而在MDA - MB - 231细胞中，Rac1、stathmin和EB1过表达。用小干扰RNA敲低Rac1或stathmin可消除IGF-I诱导的MDA - MB - 231细胞侵袭；然而，敲低EB1则不能，这表明Rac1和stathmin而非EB1对于侵袭是必需的。导致细胞侵袭的信号通路可能并不相同，但共享一些共同分子，通过片状伪足形成导致细胞迁移。
