title: WAVE2, N-WASP, and Mena facilitate cell invasion via phosphatidylinositol 3-kinase-dependent local accumulation of actin filaments.
abstract: Cell migration is accomplished by the formation of cellular protrusions such as lamellipodia and filopodia. These protrusions result from actin filament (F-actin) rearrangement at the cell cortex by WASP/WAVE family proteins and Drosophila enabled (Ena)/vasodilator-stimulated factor proteins. However, the role of each of these actin cytoskeletal regulatory proteins in the regulation of three-dimensional cell invasion remains to be clarified. We found that platelet-derived growth factor (PDGF) induces invasion of MDA-MB-231 human breast cancer cells through invasion chamber membrane pores. This invasion was accompanied by intensive F-actin accumulation at the sites of cell infiltration. After PDGF stimulation, WAVE2, N-WASP, and a mammalian Ena (Mena) colocalized with F-actin at the sites of cell infiltration in a phosphatidylinositol 3-kinase (PI3K)-dependent manner. Depletion of WAVE2, N-WASP, or Mena by RNA interference (RNAi) abrogated both cell invasion and intensive F-actin accumulation at the invasion site. These results indicate that by mediating intensive F-actin accumulation at the sites of cell infiltration, WAVE2, N-WASP, and Mena are crucial for PI3K-dependent cell invasion induced by PDGF.
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, Yokohama 241-0815, Japan. ktaka@gancen.asahi.yokohama.jp
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Takahashi
authors.forename: Katsuo
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000199:Actins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008840:Microfilament Proteins / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D034622:RNA Interference; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000502:physiology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000502:physiology*
chemical_list: D000199:Actins; C511939:Enah protein, human; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; C120152:WASF2 protein, human; C495771:WASL protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D019869:Phosphatidylinositol 3-Kinases