title: Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer.
abstract: Studies on a variety of cell lines have shown that p120-catenin can directly regulate the stability of E-cadherin complexes and control the activity of small GTPases to influence cell adhesion. Despite this data, clinical studies of human solid tumors have not been reported to investigate these protein interactions. To explore the correlation between p120-catenin, E-cadherin, and small GTPases in human lung cancer, we examined the expression patterns of p120-catenin, E-cadherin, RhoA, Cdc42, and Rac1, and their prognostic significance in 138 patients with non-small cell lung cancer (NSCLC). While normal bronchial epithelium showed strong membrane expression of p120-catenin and E-cadherin, lung cancer tissues had reduced membrane expression and ectopic cytoplasmic expression of p120-catenin and E-cadherin. Expression of RhoA, Cdc42, and Rac1 was also found to be higher in tumor tissue than in normal lung tissue. A correlation between abnormal p120-catenin, E-cadherin expression, and overexpression of specific small GTPases was also associated with poor differentiation, high TNM stage, and lymph node metastasis in NSCLC patients. We also used an in vitro model to evaluate their expression, and to determine whether protein expression correlated with the invasive capacity of lung cancer cell lines. Consistent with our in vivo data, abnormal expression of p120-catenin and E-cadherin with overexpression of specific small GTPases were significantly associated with the high metastatic capacity of BE1 cells. Based on our results, we conclude that abnormal p120-catenin expression correlates with abnormal E-cadherin expression and specific small GTPase overexpression, which contribute to the malignancy-related to NSCLC.
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peng-Xin
authors.initials: PX
authors.lastname: Zhang
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Jiang
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Xu-Yong
authors.initials: XY
authors.lastname: Lin
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Yang
authors.forename: Qing-Chang
authors.initials: QC
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D012334:RNA, Neoplasm; D020559:Monomeric GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human