Overexpression of JAM-A in Non-Small Cell Lung Cancer Correlates with Tumor Progression

Min Zhang,Wenting Luo,Bo Huang,Xueshan Qiu,Qingfu Zhang,Limei Sun,Zihui Liu,Enhua Wang,Ke Xu,Srikumar P Chellappan

doi:10.1371/journal.pone.0079173

Abstract

The objective of the current study was to determine the clinical significance of junctional adhesion molecule A (JAM-A) in patients with non-small cell lung cancer (NSCLC) and the biological function of JAM-A in NSCLC cell lines. We showed that JAM-A is predominantly expressed in cell membranes and high expression of JAM-A occurred in 37% of lung tumor specimens compared to corresponding normal tissues. High expression of JAM-A was significantly correlated with TNM stage (P = 0.021), lymph node metastasis (P = 0.007), and decreased overall survival (P = 0.02), In addition, we observed that silencing JAM-A by small interfering RNA inhibited tumor cell proliferation and induced cell cycle arrest at the G1/S boundary. Western blotting analysis revealed that knockdown of JAM-A decreased the protein levels of cyclin D1, CDK4, 6, and P-Rb. Thus, JAM-A plays an important role in NSCLC progression.

Highlights

Junctional adhesion molecule A (JAM-A) is a type I transmembrane glycoprotein that belongs to the immunoglobulin superfamily
We showed that JAM-A is expressed relatively high amounts in non-small cell lung cancer (NSCLC) tissues and some types of NSCLC cell lines, and that cell membrane-associated JAM-A levels are correlated with tumor aggressiveness
JAM-A was predominantly expressed in cell membranes; high expression of JAM-A was found in 37% of lung tumor specimens (Table 1), which was much higher than bronchial epithelia and pneumocytes in corresponding nontumorous lung tissues (Fig. 1)

Summary

Introduction

Junctional adhesion molecule A (JAM-A) is a type I transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Naik et al [18] initially reported that JAM-A could reduce invasion and motility of breast cancer cell lines in vitro and JAM-A expression in breast cancer patients was negatively associated with tumor aggressiveness and metastasis. Mc Sherry et al [21], using a larger clinical data set, reported a positive correlation between JAM-A expression and invasive breast cancer prognosis. Larger clinical-, in vitro-, and in vivogenerated data sets were recently reported in breast cancer and epidermoid carcinoma [22,23,24,25,26]. We determined the association between JAM-A expression and proliferation in several NSCLC cell lines. We showed that JAM-A is expressed relatively high amounts in NSCLC tissues and some types of NSCLC cell lines, and that cell membrane-associated JAM-A levels are correlated with tumor aggressiveness

Objectives

Methods

Results

Conclusion