Plakophilin-2 accelerates cell proliferation and migration through activating EGFR signaling in lung adenocarcinoma

• Published in: Pathology, research and practice research and practice, 2019-07, Vol.215 (7), p.152438, Article 152438
• Main Authors: Hao, Xiang-Lin, Tian, Zhen, Han, Fei, Chen, Jian-Ping, Gao, Li-Yun, Liu, Jin-Yi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Animals; Cell Line, Tumor; Cell migration; Cell Movement - physiology; Cell proliferation; Cell Proliferation - physiology; Disease Progression; EGFR signaling pathway; ErbB Receptors - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Lung - metabolism; Lung - pathology; Lung adenocarcinoma; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Mice; Mice, Nude; Middle Aged; PKP2; Plakophilins - metabolism; Prognosis; Sex Factors; Signal Transduction - physiology; Survival Rate
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2019.152438

•The first study to explore the expression and clinical significance of PKP2 in non-small cell lung cancer.•The clinical significance of PKP2 between lung adenocarcinoma and lung squamous carcinoma are different.•PKP2 expression is associated with EGFR signaling pathway in lung adenocarcinoma, but not in lung squamous carcinoma. Plakophilin 2 (PKP2), encodes a plakophilin protein that belongs to the member of desmosomal proteins. It has been reported that high expression of PKP2 is associated with several types of cancer in humans. However, the role of PKP2 in lung cancer remains obscure. PKP2 expression was investigated in non-small cell lung cancer (NSCLC) tissues and non-tumor tissues by performing immunohistochemistry on a tissue microarray and using The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis and multivariate Cox-regression analysis were performed to identify the clinical significance of PKP2. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), colony formation, Transwell and xenograft tumor growth/ metastasis assays were conducted to evaluate the biological function of PKP2 in vitro and in vivo. Gene set enrichment analysis (GSEA), WB and immunoprecipitation (IP) assay were utilized to explore the potential downstream signaling pathway and molecule mechanism of PKP2 in lung adenocarcinoma (LUAD). Analysis of PKP2 expression and clinicopathological parameters reveals a significant correlation of PKP2 expression with gender (n = 1020, P