Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

摘要: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)) has anti-cancer activity in several colon cancers. 1α,25(OH)(2)D(3) induces the epithelial differentiation of SW480 cancer cells expressing VDR (SW480-ADH) upregulating E-cadherin expression; however, precise mechanism remains unknown. We found phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKIIβ) but not PIPKIIα is required for VDR-mediated induction SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology phospholipase C-delta1 (PLCδ1 PHD) possess high affinity phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) mainly localized to nucleus plasma membrane, respectively. expression PDZ PLCδ1 PHD inhibited 1α,25(OH)(2)D(3)-induced upregulation, suggesting nuclear PI(4,5)P(2) production mediates through PIPKIIβ a VDR-dependent manner. also involved suppression cell motility 1α,25(OH)(2)D(3). These results PIPKIIβ-mediated important upregulation inhibition cellular activation.