Claudin 18.2 Inhibits the Proliferation of Small-Cell Lung Cancer Cells via G0/G1 Cell-Cycle Arrest

Abstract

Claudin (CLDN) 18.2, a member of the CLDN family, contains tight junctions that regulate the physiological functions of epithelial cells, such as cell differentiation, proliferation, and polarity. CLDN18.2 is also expressed, and performs various functions, in several cancers; however, its expression and function in small-cell lung cancer (SCLC) have not been elucidated. Herein, we determined the expression of CLDN18.2 in SCLC cell lines using quantitative RT-PCR and western blotting. Moreover, we established inducible CLDN18.2 expression SCLC cells and CLDN18.2 knockout SCLC cells and showed that CLDN18.2 inhibited the proliferation of SCLC via G0/G1 cell-cycle arrest using cell-proliferation assay and cell-cycle analysis. This cell-cycle arrest was caused by downregulation of CCND1 and induction of CDKN1A. The present study evokes research interest in CLDN18.2 as a potential therapeutic target and prognostic marker in SCLC, paving the way for future research prospects.