Increased expression of claudin‑12 promotes the metastatic phenotype of human bronchial epithelial cells and is associated with poor prognosis in lung squamous cell carcinoma

Sun,Lemeng; Feng,Liangshu; Cui,Jiuwei

doi:10.3892/etm.2018.6964

Increased expression of claudin‑12 promotes the metastatic phenotype of human bronchial epithelial cells and is associated with poor prognosis in lung squamous cell carcinoma

Authors:
- Lemeng Sun
- Liangshu Feng
- Jiuwei Cui
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Affiliations: Department of Oncology, Stem Cell and Cancer Center, The First Bethune Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurology and Neuroscience Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: November 13, 2018 https://doi.org/10.3892/etm.2018.6964
Pages: 165-174
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A prior study by our group using cDNA array analysis identified the tight junction component claudin‑12 (CLDN12) to be an upregulated gene in lung squamous cell carcinoma (SqCC) cells compared with normal human bronchial epithelial cells. The present study aimed to explore the effect and underlying molecular mechanism of CLDN12 with regard to the malignant phenotype of SqCC. Firstly, the expression patterns of CLDN12 in SqCC tissues, lung adenocarcinoma tissues and histologically non‑neoplastic lung epithelial tissues were investigated by immunohistochemistry and western blotting. Additionally, associations between CLDN12 expression and clinicopathological indicators were examined in patients with SqCC. Furthermore, the impact of CLDN12 on the malignant phenotype of the human bronchial epithelial cell line BEAS‑2B in vitro was assessed using the Cell Counting kit‑8 assay, Transwell assay and a wound‑healing experiment. Western blotting and immunofluorescence were also used to detect the impact of CLDN12 on the epithelial‑mesenchymal transition (EMT) of BEAS‑2B cells. Tyrosine kinase 2 (Tyk2) RNA interference was further utilized to determine the impact of the Tyk2/signal transducer and activator of transcription 1 (Stat1) signaling pathway on the EMT of BEAS‑2B cells. To conclude, it was indicated that the expression of CLDN12 was upregulated in SqCC tissues and was associated with the extent of lymphatic metastasis in patients with SqCC. Furthermore, CLDN12 promoted the EMT of human bronchial epithelial cells in vitro. The findings indicated that the induction of Tyk2/Stat1 signaling appears to be an important mechanism by which CLDN12 promotes the EMT of SqCC cells.

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