Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells.
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.
Suzuki
Katsuo
K
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
Takahashi
Kazuhide
K
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C107953:RAC1 protein, human; D020703:ras GTPase-Activating Proteins; C076744:cytoplasmic linker protein 170; D016547:Kinesins; D020830:rac1 GTP-Binding Protein