title: Forkhead box L1 is frequently downregulated in gallbladder cancer and inhibits cell growth through apoptosis induction by mitochondrial dysfunction.
abstract: BACKGROUND
  Forkhead box L1 (FOXL1), considered as a novel candidate tumor suppressor, suppresses proliferation and invasion in certain cancers. However, the regulation and function of FOXL1 in gallbladder cancer (GBC) remains unclear.
  
  
  METHODS
  FOXL1 expression at mRNA and protein levels in GBC tissues and cell lines were examined by RT-PCR, immunohistochemistry and western blot assay. FOXL1 expression in GBC cell lines was up-regulated by transfection with pcDNA-FOXL1. The effects of FOXL1 overexpression on cell proliferation, apoptosis, migration and invasion were evaluated in vitro or in vivo. In addition, the status of mediators involved in migration, invasion and apoptosis was examined using western blot after transfection with pcDNA-FOXL1.
  
  
  RESULTS
  FOXL1 was frequently downregulated in GBC tissues and cell lines. Its higher expression is associated with better prognosis, while its lower expression is correlated with advanced TNM stage and poor differentiation. FOXL1 overexpression in NOZ cells significantly suppresses cell proliferation, migration and invasion in vitro and tumorigenicity in nude mice. FOXL1 overexpression disrupted mitochondrial transmembrane potential and triggered mitochondria-mediated apoptosis in NOZ cells. In addition, FOXL1 overexpression suppressed ZEB1 expression and induced E-cadherin expression in NOZ cells.
  
  
  CONCLUSIONS
  Our findings suggested that dysregulated FOXL1 is involved in tumorigenesis and progression of GBC and may serve as a predictor of clinical outcome or even a therapeutic target for patients with GBC.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Mingdi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Quan
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008819:Mice, Nude; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C491001:FOXL1 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D045304:Cytochromes c; D020169:Caspases