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
リソース情報
ヒト・動物細胞 A549