ck-0944636 and Prostatic-Neoplasms

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.. 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.. 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.. 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.

Topics: Actin Cytoskeleton; Actin-Related Protein 2-3 Complex; Actins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Knockdown Techniques; Humans; Indoles; Male; Neoplasm Invasiveness; Phenotype; Phosphorylation; Polymerization; Prostatic Neoplasms; Protein Binding; RNA Interference; Signal Transduction; Thiophenes; Tyrosine; Wiskott-Aldrich Syndrome Protein Family