論文 - 詳細
| RRC ID | 37555 |
|---|---|
| 著者 | Ikari A, Taga S, Watanabe R, Sato T, Shimobaba S, Sonoki H, Endo S, Matsunaga T, Sakai H, Yamaguchi M, Yamazaki Y, Sugatani J. |
| タイトル | Clathrin-dependent endocytosis of claudin-2 by DFYSP peptide causes lysosomal damage in lung adenocarcinoma A549 cells. |
| ジャーナル | Biochim Biophys Acta |
| Abstract |
Claudins are tight junctional proteins and comprise a family of over 20 members. Abnormal expression of claudins is reported to be involved in tumor progression. Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases cell proliferation, whereas it is not expressed in normal tissues. Claudin-2-targeting molecules such as peptides and small molecules may be novel anti-cancer drugs. The short peptide with the sequence DFYSP, which mimics the second extracellular loop of claudin-2, decreased claudin-2 content in the cytoplasmic fraction of A549 cells. In contrast, it did not affect the content in the nuclear fraction. The decrease in claudin-2 content was inhibited by chloroquine (CQ), a lysosomal inhibitor, but not by MG-132, a proteasome inhibitor. In the presence of DFYSP peptide and CQ, claudin-2 was co-localized with LAMP-1, a lysosomal marker. The DFYSP peptide-induced decrease in claudin-2 content was inhibited by monodancylcadaverine (MDC), an inhibitor of clathrin-dependent endocytosis. DFYSP peptide increased lysosome content and cathepsin B release, and induced cellular injury, which were inhibited by MDC. Cellular injury induced by DFYSP peptide was inhibited by necrostatin-1, an inhibitor of necrotic cell death, but not by Z-VAD-FMK, an inhibitor of apoptotic cell death. Our data indicate that DFYSP peptide increases the accumulation of the peptide and claudin-2 into the lysosome, resulting in lysosomal damage. Claudin-2 may be a new target for lung cancer therapy. |
| 巻・号 | 1848(10 Pt A) |
| ページ | 2326-36 |
| 公開日 | 2015-10-1 |
| DOI | 10.1016/j.bbamem.2015.07.003 |
| PII | S0005-2736(15)00225-4 |
| PMID | 26163137 |
| MeSH | Apoptosis / drug effects Cell Line, Tumor Clathrin / metabolism* Claudin-2 / metabolism* Dose-Response Relationship, Drug Endocytosis / drug effects Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology* Lysosomes / drug effects Lysosomes / metabolism* Lysosomes / pathology Peptides / administration & dosage* |
| IF | 3.411 |
| 引用数 | 5 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | A549 |