Abstract
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 IIIβ, 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.
Highlights
Phosphoinositides are lipid constituents of plasma and organelle membranes and comprise seven different phosphorylated versions
To identify the physiologic role of PI[4]P in the Golgi apparatus during tumor progression, we investigated the effects of PI[4]P metabolism on cell–cell adhesion and cell migration in breast cancer cells
To obtain insights into the role of phosphoinositide metabolism in the regulation of cell– cell adhesion, we investigated the effect of siRNA-mediated depletion of all phosphoinositide phosphatase isoforms in MCF7 cells (Fig. 1)
Summary
Phosphoinositides are lipid constituents of plasma and organelle membranes and comprise seven different phosphorylated versions. The levels of various phosphorylated phosphoinositides within the cell are regulated by multiple phosphoinositide kinases and phosphoinositide phosphatases [1, 2]. Phosphatidylinositol 4-phosphate [PI[4]P] is a relatively abundant phosphoinositide required for the maintenance and function of the Golgi apparatus, including intracellular trafficking [3]. The PI[4]P level at the Golgi apparatus is controlled by phosphatidylinositol 4-kinases (PI4K) and SAC1 phosphoinositide phosphatase. The PI4K isoforms phosphatidylinositol 4-kinase IIa (PI4KIIa) and PI4KIIIb are known to localize to the Golgi apparatus and to be involved in membrane transport from the trans-Golgi network to the plasma membrane [4, 5].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
