title: Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells.
abstract: Epidermal growth factor receptor (EGFR) activation has been shown to play a critical role in tumor angiogenesis. In this study, we investigate the correlation between EGFR mutations and cadherin-5 (CDH5), which is an angiogenic factor, in lung cancer cells. Increased expression CDH5 is observed in lung cancer cells with EGFR mutations. Stable lung cancer cell lines expressing mutant (exon 19 deletion E746-A750, and exon 21 missense mutation L858R) and wild type EGFR genes are established. A significantly higher expression of CDH5 is observed in exon 19 deletion stable lung cancer cells and mouse xenografts. Further studies show that expression of CDH5 is decreased after the inhibition of EGFR and downstream Akt pathways in lung cancer cells with EGFR mutation. In addition, mutant EGFR genes potentiates angiogenesis in lung cancer cells, which is inhibited by CDH5 siRNA, and potentiates migration and invasion in lung cancer cells. Our study shows that mutant EGFR genes are associated with overexpression of CDH5 through increased phosphorylation of EGFR and downstream Akt pathways. Our result may provide an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future.
authors.affiliation: Department of Thoracic Oncology, Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.|Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan.
authors.forename: Ming-Szu
authors.initials: MS
authors.lastname: Hung
authors.affiliation: Department of Emergency Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: I-Chuan
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Jr-Hau
authors.initials: JH
authors.lastname: Lung
authors.affiliation: Department of Anatomic Pathology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Paul-Yann
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Thoracic Oncology, Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Thoracic Oncology, Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.|Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
mesh_terms: D000072283:A549 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation / Q000502:physiology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D000099152:Cadherin 5; C512478:EGFR protein, human