title: Zbed3 contributes to malignant phenotype of lung cancer via regulating β-catenin and P120-catenin 1.
abstract: Our previous studies indicate that abnormal expression of several Wnt signaling molecules including Axin, Dvl and β-catenin are involved in proliferation, invasion and metastasis of lung cancer. Zbed3 was found to inhibit function of Axin-GSK3β complex and thus lead to accumulation of β-catenin in NIH3T3 and HEK293T cells. However its function in malignant tumors is largely unknown. Here we investigate the clinico-pathological significance of Zbed3 expression and its function in non-small cell lung cancer. We use immunohistochemistry and Western blotting to examine Zbed3 expression in non-small cell lung cancer and lung tissues. Transfection of siRNA and plasmid was used to study the function of Zbed3 in lung cancer cells in vitro. We found Zbed3 expression was elevated in cancer tissues compared to normal lung tissues. Increased Zbed3 expression is significantly associated with lymph node metastasis, advanced TNM stages, higher Ki67 status and patients' poor clinical outcome. Higher Zbed3 expression was also found in lung cancer cell lines compared to bronchial epithelial cell line HBE. Downregulation of Zbed3 by siRNA significantly inhibits cancer cell proliferation and invasion in vitro. Downregulation of Zbed3 also significantly inhibits expression of β-catenin, downstream molecules of Wnt signaling and P120ctn-1 in lung cancer cells. These results suggest that Zbed3 may contribute to lung cancer cell invasion through regulating β-catenin and p120ctn-1 and may be a promissing cancer marker in non-small cell lung cancer.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Chuifeng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Xuyong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Luan
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D051177:Catenins / Q000502:physiology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D051177:Catenins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C540253:ZBED3 protein, human
keywords: NSCLC; Zbed3; p120ctn-1; β-catenin