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.
CONCLUSIONS - 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.
Anticancer research. 2016 Mar [Epub]
Hoi Ping Weeks, Andrew J Sanders, Howard G Kynaston, Wen G Jiang
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K., Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K., Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, U.K., Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.