title: Impact of p120-catenin isoforms 1A and 3A on epithelial mesenchymal transition of lung cancer cells expressing E-cadherin in different subcellular locations.
abstract: The epithelial mesenchymal transition (EMT) is an important process in tumor development. Despite previous investigations, it remains unclear how p120-catenin (p120ctn) isoforms 1A and 3A affect the EMT of tumor cells. Here we investigated expression of p120ctn, E-cadherin and vimentin in 78 human non-small cell lung cancer (NSCLC) samples by immunohistochemistry and found that p120ctn membrane expression positively correlated with E-cadherin expression (P<0.001) and negatively correlated with vimentin expression and lymph node metastasis (P<0.05). Meanwhile, p120ctn cytoplasmic expression negatively correlated with E-cadherin expression (P<0.001) and positively correlated with vimentin expression and lymph node metastasis (P<0.05). Cells expressing high (H460 and SPC) and low (H1299 and LK2) levels of p120ctn were screen to investigate its impact on EMT. E-cadherin was restricted to the cell membrane in H460 and H1299 cells, whereas it was expressed in the cytoplasm of SPC and LK2 cells. Ablation of endogenous p120ctn isoform 1A in cells expressing high levels of the protein resulted in decreased E-cadherin expression, increased N-cadherin, vimentin and snail expression and enhanced invasiveness in H460 cells. Meanwhile, completely opposite results were observed in SPC cells. Furthermore, transfection of in H1299 cells expressing low p120ctn levels with the p120ctn isoform 1A plasmid resulted in increased E-cadherin expression, decreased N-cadherin, vimentin and snail expression and weakened invasiveness, while LK2 cells showed completely opposite results. Both cell lines expressing low p120ctn levels and transfected with the p120ctn isoform 3A plasmid appeared to have increased E-cadherin expression, decreased N-cadherin, vimentin and snail expression and weakened invasiveness. In conclusion, in cells with membrane E-cadherin, both p120ctn isoforms 1A and 3A inhibited EMT and decreased cell invasiveness. In cells with cytoplasmic E-cadherin, p120ctn isoform 1A promoted EMT and increased cell invasiveness, while p120ctn isoform 3A inhibited the EMT and decreased cell invasiveness.
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Yijun
authors: Y
authors: Zhang
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Yue
authors: Y
authors: Zhao
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Guiyang
authors: G
authors: Jiang
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Xiupeng
authors: X
authors: Zhang
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Huanyu
authors: H
authors: Zhao
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Junhua
authors: J
authors: Wu
authors: Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors: Ke
authors: K
authors: Xu
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors: Enhua
authors: E
authors: Wang
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D015820:Cadherins / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D051177:Catenins / Q000235:genetics*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000473:pathology; D003593:Cytoplasm / Q000235:genetics / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics*; D014746:Vimentin / Q000235:genetics; D000095002:Delta Catenin
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D051177:Catenins; D020033:Protein Isoforms; D014746:Vimentin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human