Phosphatidylinositol 4-phosphate in the Golgi apparatus regulates cell-cell adhesion and invasive cell migration in human breast cancer

Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels une sous-expression de PI4P dans l'appareil de Golgi des cellules de cancer du sein favorise la progression tumorale

Résumé en anglais

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 (PI4P) in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI4P 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 IIIβ (PI4KIIIβ), which generates PI4P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI4P effector, Golgi phosphoprotein 3 (GOLPH3), 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 PI4P levels in the Golgi apparatus.