Biochimica et Biophysica Acta 2014-09-01

Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

Akira Ikari, Ryo Watanabe, Tomonari Sato, Saeko Taga, Shun Shimobaba, Masahiko Yamaguchi, Yasuhiro Yamazaki, Satoshi Endo, Toshiyuki Matsunaga, Junko Sugatani

文献索引：Biochim. Biophys. Acta 1843(9) , 2079-88, (2014)

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摘要

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. Copyright © 2014 Elsevier B.V. All rights reserved.