RRC ID 45113
Author Ikari A, Watanabe R, Sato T, Taga S, Shimobaba S, Yamaguchi M, Yamazaki Y, Endo S, Matsunaga T, Sugatani J.
Title Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.
Journal Biochim Biophys Acta
Abstract Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.
Volume 1843(9)
Pages 2079-88
Published 2014-9-1
DOI 10.1016/j.bbamcr.2014.05.017
PII S0167-4889(14)00202-X
PMID 24907662
MeSH Adenocarcinoma / metabolism* Adenocarcinoma / pathology* Adenocarcinoma of Lung CCAAT-Enhancer-Binding Proteins / metabolism Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Nucleus / drug effects Cell Nucleus / metabolism* Cell Proliferation / drug effects Claudins / metabolism* Colforsin / pharmacology Cyclin D1 / metabolism G1 Phase / drug effects Gene Knockdown Techniques Heat-Shock Proteins / metabolism Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology* Mutant Proteins / metabolism Nuclear Export Signals Nuclear Localization Signals / metabolism Phosphorylation / drug effects S Phase / drug effects Time Factors Zonula Occludens-1 Protein / metabolism
IF 3.79
Times Cited 38
Human and Animal Cells