title: TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the Wnt/β-catenin pathway.
abstract: BACKGROUND
  The thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue naturally disordered protein that has been found to be associated with thyroid, gastric, and breast cancer. A recent study has indicated that the protein functions as a positive regulator in the Wnt/β-catenin signaling pathway in human breast cancer. However, no research has been done in the area of lung cancer. Therefore, the goal of the present study was to confirm the relationship among TC-1, lung cancer, and the Wnt/β-catenin signaling pathway.
  
  
  METHODS
  The expression of TC-1 was immunohistochemically examined in 147 patients with non-small-cell lung cancer. TC-1-overexpressed and silenced A549 cells were infected using lentivirus and MTT cell proliferation analysis, and Matrigel invasion assays and scratch-wound assays were performed to confirm the biologic behavioral changes in different A549 cell subsets. The Wnt/β-catenin signaling pathway, key gene β-catenin, target genes of vascular endothelial growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were tested at the mRNA and protein level.
  
  
  RESULTS
  TC-1 was detected in 97 of the 147 non-small-cell lung cancer primary tumor specimens, and its expression correlated with the TNM stage and regional lymph node metastasis (P < 0.01). In vitro experiments demonstrated that TC-1 expression affected both proliferation and invasion in the A549 cell line. Furthermore, expression of TC-1 protein affected the Wnt/β-catenin signaling pathway's downstream genes, such as vascular endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein level.
  
  
  CONCLUSIONS
  TC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Su
authors.forename: Lijun
authors.initials: L
authors.lastname: Huang
authors.forename: Wenhai
authors.initials: W
authors.lastname: Li
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yan
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Zhang
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
authors.forename: Jie
authors.initials: J
authors.lastname: Lei
authors.forename: Guangzhen
authors.initials: G
authors.lastname: Ba
authors.forename: Boya
authors.initials: B
authors.lastname: Liu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C418741:TCIM protein, human; D051176:beta Catenin
keywords: Cancer metastasis; Lung cancer; TC-1; Wnt/β-catenin