RRC ID 51647
Author Shimobaba S, Taga S, Akizuki R, Hichino A, Endo S, Matsunaga T, Watanabe R, Yamaguchi M, Yamazaki Y, Sugatani J, Ikari A.
Title Claudin-18 inhibits cell proliferation and motility mediated by inhibition of phosphorylation of PDK1 and Akt in human lung adenocarcinoma A549 cells.
Journal 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.
Volume 1863(6 Pt A)
Pages 1170-8
Published 2016-6
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 3.79
Times Cited 16
Human and Animal Cells RERF-LC-AI(RCB0444) IA-LM(RCB0554) WA-hT(RCB2279)