論文 - 詳細
| RRC ID | 51647 |
|---|---|
| 著者 | Shimobaba S, Taga S, Akizuki R, Hichino A, Endo S, Matsunaga T, Watanabe R, Yamaguchi M, Yamazaki Y, Sugatani J, Ikari A. |
| タイトル | Claudin-18 inhibits cell proliferation and motility mediated by inhibition of phosphorylation of PDK1 and Akt in human lung adenocarcinoma A549 cells. |
| ジャーナル | Biochim Biophys Acta |
| Abstract |
Abnormal expression of claudin subtypes has been reported in various cancers. However, the pathological role of each claudin has not been clarified in detail. Claudin-18 was absent in human non-small cell and small cell lung cancers, although it is expressed in normal lung tissues. Here, we examined the effect of claudin-18 expression on the expression of junctional proteins, cell proliferation, and cell motility using human lung adenocarcinoma A549 cells. Real-time PCR and western blotting showed that exogenous expression of claudin-18 had no effect on the expression of junctional proteins including claudin-1, zonula occludens-1 (ZO-1), occludin, and E-cadherin. Claudin-18 was mainly distributed in cell-cell contact areas concomitant with ZO-1. Cell proliferation was significantly decreased at 48 and 72h after seeding of claudin 18-expressing cells. Claudin-18 suppressed cell motility, whereas it increased cell death in anoikis. Claudin-18 decreased phosphorylated (p)-3-phosphoinositide-dependent protein kinase-1 (PDK1) and p-Akt levels without affecting p-epidermal growth factor receptor and p-phosphatidylinositol-3 kinase (PI3K) levels. Furthermore, claudin-18 was bound with PDK1 and suppressed the nuclear localization of PDK1. We suggest that claudin-18 suppresses the abnormal proliferation and motility of lung epithelial cells mediated by inhibition of the PI3K/PDK1/Akt signaling pathway. |
| 巻・号 | 1863(6 Pt A) |
| ページ | 1170-8 |
| 公開日 | 2016-6-1 |
| DOI | 10.1016/j.bbamcr.2016.02.015 |
| PII | S0167-4889(16)30040-4 |
| PMID | 26919807 |
| MeSH | Adenocarcinoma / genetics Adenocarcinoma / metabolism Adenocarcinoma / pathology Anoikis / drug effects Anoikis / physiology Cell Line, Tumor Cell Membrane Permeability Cell Movement / drug effects Cell Movement / physiology* Cell Proliferation / drug effects Cell Proliferation / physiology* Chromones / pharmacology Claudins / genetics Claudins / metabolism* Enzyme Inhibitors / pharmacology Gene Expression Regulation, Neoplastic Humans Immunoblotting Lung Neoplasms / genetics Lung Neoplasms / metabolism Lung Neoplasms / pathology Microscopy, Confocal Morpholines / pharmacology Phosphatidylinositol 3-Kinases / metabolism Phosphoinositide-3 Kinase Inhibitors Phosphorylation Protein Serine-Threonine Kinases / metabolism* Proto-Oncogene Proteins c-akt / metabolism* Pyruvate Dehydrogenase Acetyl-Transferring Kinase Reverse Transcriptase Polymerase Chain Reaction Tight Junction Proteins / genetics Tight Junction Proteins / metabolism Tight Junctions / metabolism |
| IF | 3.411 |
| 引用数 | 16 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RERF-LC-AI(RCB0444) IA-LM(RCB0554) WA-hT(RCB2279) |