title: Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells.
abstract: 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 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKIIβ) but not PIPKIIα is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLCδ1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLCδ1 PHD inhibited 1α,25(OH)(2)D(3)-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P(2) production mediates E-cadherin expression through PIPKIIβ in a VDR-dependent manner. PIPKIIβ is also involved in the suppression of the cell motility induced by 1α,25(OH)(2)D(3). These results indicate that PIPKIIβ-mediated PI(4,5)P(2) signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.
authors.affiliation: Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo, Japan. zkouchi@toyaku.ac.jp
authors.forename: Zen
authors.initials: Z
authors.lastname: Kouchi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Fukami
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D055785:Gene Knockdown Techniques; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D015820:Cadherins; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase