CLIP-170对侵袭性人乳腺癌细胞中片状伪足形成和细胞侵袭的调控
Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells.
作者信息
Suzuki Katsuo, Takahashi Kazuhide
机构信息
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
出版信息
Biochem Biophys Res Commun. 2008 Apr 4;368(2):199-204. doi: 10.1016/j.bbrc.2008.01.069. Epub 2008 Jan 29.
Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1-CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1-CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1.
Rac1调控细胞侵袭所必需的片状伪足形成。我们在此报告，在侵袭性人乳腺癌细胞中，HGF和血清分别显著促进了片状伪足形成和三维侵袭。在血清饥饿的细胞中，Rac1与CLIP - 170、IQGAP1和驱动蛋白形成复合物，用HGF和血清刺激细胞会导致IQGAP1和驱动蛋白从Rac1 - CLIP - 170复合物中部分释放。PI3K抑制剂抑制了HGF诱导的蛋白质释放和片状伪足形成的促进作用。此外，通过siRNA下调CLIP - 170可使IQGAP1和驱动蛋白从Rac1中释放，并促进片状伪足形成和侵袭，这与HGF和血清无关。结果表明，HGF或血清促进片状伪足形成和侵袭需要PI3K依赖的IQGAP1和驱动蛋白从Rac1 - CLIP - 170复合物中释放，并且CLIP - 170通过将IQGAP1和驱动蛋白拴系到Rac1上，防止细胞发生不依赖细胞外刺激的片状伪足形成和侵袭。
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