Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell-Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4) P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4) P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIb, which generates PI(4) P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4) P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4) P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4) P levels in the Golgi apparatus.