Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells
Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells
复制标题
DOI：
10.1016/j.bbrc.2011.04.045
复制
发表时间：
2011-05-20
影响因子：
3.1
通讯作者：
Fukami, Kiyoko
中科院分区：
文献类型：
--
作者：
Kouchi, Zen;Fujiwara, Yuki;Fukami, Kiyoko
大量流行病学数据表明，维生素D受体（VDR）由其配体或活性代谢产物1α,25 - 二羟基维生素D - 3（1α,25(OH)₂D - 3）诱导的信号通路在多种结肠癌中具有抗癌活性。1α,25(OH)₂D - 3通过上调E - 钙黏蛋白的表达，诱导表达VDR的SW480结肠癌细胞（SW480 - ADH）发生上皮分化；然而，其确切机制仍不明确。我们发现，在SW480 - ADH细胞中，VDR介导的E - 钙黏蛋白诱导过程需要磷脂酰肌醇 - 5 - 磷酸4 - 激酶IIβ型（PIPKIIβ），而非PIPKIIα。突触后密度蛋白/盘状大蛋白/紧密连接蛋白（PDZ）结构域的syntenin - 2以及磷脂酶C - δ1（PLCδ1）的普列克底物蛋白同源结构域（PHD）分别对主要定位于细胞核和质膜的磷脂酰肌醇 - 4,5 - 二磷酸（PI(4,5)P₂）具有高亲和力。表达syntenin - 2的PDZ结构域而非PLCδ1的PHD结构域，会抑制1α,25(OH)₂D - 3诱导的E - 钙黏蛋白上调，这表明细胞核内PI(4,5)P₂的生成以VDR依赖的方式通过PIPKIIβ介导E - 钙黏蛋白的表达。PIPKIIβ还参与1α,25(OH)₂D - 3诱导的细胞运动抑制过程。这些结果表明，PIPKIIβ介导的PI(4,5)P₂信号通路对于VDR激活诱导的E - 钙黏蛋白上调和细胞运动抑制至关重要。（C）2011爱思唯尔公司版权所有。
Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) has anti-cancer activity in several colon cancers. 1 alpha,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 (PIPKII beta) but not PIPKII alpha 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 (PLC delta 1 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 PLC delta 1 PHD inhibited 1 alpha,25(OH)(2)D-3-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P-2 production mediates E-cadherin expression through PIPKII beta in a VDR-dependent manner. PIPKII beta is also involved in the suppression of the cell motility induced by 1 alpha,25(OH)(2)D-3. These results indicate that PIPKII beta-mediated PI(4,5)P-2 signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation. (C) 2011 Elsevier Inc. All rights reserved.