Anticancer research · 2016
The Association Between WAVE1 and -3 and the ARP2/3 Complex in PC 3 Cells.
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Weeks Hoi Ping, Sanders Andrew J, Kynaston Howard G, Jiang Wen G
Аннотация
BACKGROUND: Actin polymerisation is stimulated by the actin-related protein (ARP) 2/3 complex and drives cell migration. This complex is activated by Wiskott-Aldrich syndrome protein family (WASP) verprolin homologous protein (WAVE) proteins. WAVE1 and -3 have been implicated in the aggressiveness of metastatic prostate cancer cells.
MATERIALS AND METHODS: Cell growth, motility and invasion were analyzed in WAVE1- and WAVE3-knockdown PC-3 cells along with the ARP2/3 inhibitor, CK-0944636. Confocal microscopy was adopted to examine protein co-localisation. Immunoprecipitation approaches were used to determine protein tyrosine phosphorylation.
RESULTS: Cell growth suppression was observed with WAVE3 knockdown and ARP2/3 inhibition. Reduced cell invasion effects observed with WAVE1 knockdown appeared to be rescued by ARP2/3 inhibition. WAVE1 and WAVE3 and ARP2 co-localisation was lost in PC-3 WAVE-knockdown cells, while increased ARP2 tyrosine phosphorylation was observed with WAVE3 knockdown.
CONCLUSION: These results implicate a contributory role of WAVE1 and -3 to the metastatic phenotype of PC-3 cells through their interaction with the ARP2/3 complex.
MATERIALS AND METHODS: Cell growth, motility and invasion were analyzed in WAVE1- and WAVE3-knockdown PC-3 cells along with the ARP2/3 inhibitor, CK-0944636. Confocal microscopy was adopted to examine protein co-localisation. Immunoprecipitation approaches were used to determine protein tyrosine phosphorylation.
RESULTS: Cell growth suppression was observed with WAVE3 knockdown and ARP2/3 inhibition. Reduced cell invasion effects observed with WAVE1 knockdown appeared to be rescued by ARP2/3 inhibition. WAVE1 and WAVE3 and ARP2 co-localisation was lost in PC-3 WAVE-knockdown cells, while increased ARP2 tyrosine phosphorylation was observed with WAVE3 knockdown.
CONCLUSION: These results implicate a contributory role of WAVE1 and -3 to the metastatic phenotype of PC-3 cells through their interaction with the ARP2/3 complex.
Предметные рубрики MeSH
Actin CytoskeletonActin-Related Protein 2-3 ComplexActinsCell Line, TumorCell MovementCell ProliferationGene Knockdown TechniquesHumansIndolesMaleNeoplasm InvasivenessPhenotypePhosphorylationPolymerizationProstatic NeoplasmsProtein BindingRNA InterferenceSignal TransductionThiophenesTyrosineWiskott-Aldrich Syndrome Protein Family