title: LZTFL1 suppresses gastric cancer cell migration and invasion through regulating nuclear translocation of β-catenin.
abstract: OBJECTIVE
  Our previous work identified leucine zipper transcription factor-like 1 (LZTFL1) as a novel tumor suppressor gene, with its expression correlated with survival outcome in gastric cancer (GC) patients. This study focuses on the role of LZTFL1 in GC aggression and metastasis as well as its underlying molecular mechanisms.
  
  
  METHODS
  LZTFL1 immunohistochemical (IHC) staining on 311 paired normal/cancer tissue arrays were used to reconfirm the clinical significance of LZTFL1 expression. Transwell chamber assays were used to determine migration and invasive ability of GC cells. Gelatin zymography was employed to investigate the matrix metalloproteinases (MMPs) activity in tumor cells. Co-immunoprecipitation and Duolink in situ proximity ligation assay were used to analyze the interaction between LZTFL1 and β-catenin and the cellular localization of the interaction.
  
  
  RESULTS
  IHC results indicated that patients with high LZTFL1 expression had a longer overall survival time (58 months, 95 % CI 28-128 months) than patients with low LZTFL1 expression (27 months, 95 % CI 23-35 months; p < 0.01). The expression level of LZTFL1 is associated with the degree of cell differentiation. LZTFL1 is necessary and sufficient to inhibit the expression of molecular markers associated with epithelial-mesenchymal transition (EMT) and cellular phenotypes associated with tumor cell EMT including the migration, invasion, and the expression and activities of MMPs of tumor cells. LZTFL1 binds β-catenin in the cytoplasm of the cell and inhibited its nuclear translocation.
  
  
  CONCLUSIONS
  LZTFL1 suppresses GC cell EMT by inhibiting β-catenin nuclear translocation. Re-expression of LZTFL1 in GC cells may be a potential therapeutic means to prevent GC metastasis.
authors.affiliation: Department of Surgical Oncology and Institute of Clinical Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.forename: Jufeng
authors.initials: J
authors.lastname: Guo
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Wang
authors.forename: Jichun
authors.initials: J
authors.lastname: Zhou
authors.forename: Chenpu
authors.initials: C
authors.lastname: Xu
authors.forename: Rongyue
authors.initials: R
authors.lastname: Teng
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Chen
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C431701:LZTFL1 protein, human; D014157:Transcription Factors; D051176:beta Catenin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9