Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1843, Issue 9, Pages 2079-2088Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2014.05.017
Keywords
Adenocarcinoma; Claudin-2; Cell proliferation; Nuclear distribution
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Funding
- JSPS [23590263]
- Pharmacological Research Foundation, Tokyo
- Takeda Science Foundation
- SRI academic research grant
- Grants-in-Aid for Scientific Research [23590263] Funding Source: KAKEN
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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 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. (C) 2014 Elsevier B.V. All rights reserved.
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