Overexpression of myosin VI in prostate cancer cells enhances PSA and VEGF secretion, but has no effect on endocytosis

Tissue expression microarrays, employed to determine the players and mechanisms leading to prostate cancer development, have consistently demonstrated that myosin VI, a unique actin-based motor, is upregulated in medium-grade human prostate cancers (Dunn et al., 2006). Thus to understand the role of myosin VI in prostate cancer development, we have characterised its intracellular localisation and function in the prostate cancer cell line LNCaP. Using light and electron microscopy we identified myosin VI on Rab5-positive early endosomes as well as on recycling endosomes and the trans-Golgi network. Intracellular targeting appears to involve two myosin VI interacting proteins, GIPC and LMTK2, both of which can be co-immunoprecipitated with myosin VI from LNCaP cells. The absence of Dab2, a tumour suppressor and myosin VI binding partner, inhibits recruitment of myosin VI to endocytic structures at the plasma membrane in LNCaP cells, but interestingly has no effect on endocytosis. SiRNA-mediated down regulation of myosin VI expression results in a significant reduction in prostate-specific antigen (PSA) and vascular endothelial growth factor (VEGF) secretion in LNCaP cells. Our results suggest that in prostate cancer cells myosin VI regulates protein secretion, but the over expression of myosin VI has no major impact on clathrin-mediated endocytosis.