title: Shisa3 is associated with prolonged survival through promoting β-catenin degradation in lung cancer.
abstract: BACKGROUND
  Despite advances in treatment and prognosis of non-small cell lung cancer (NSCLC), patient outcomes are still unsatisfactory.
  
  
  OBJECTIVE
  To reduce the morbidity and mortality of patients with NSCLC, a more comprehensive understanding of mechanisms involved in cancer progression is urgently needed.
  
  
  METHODS
  By comparison of gene expression profiles in the cell line pair with differential invasion ability, CL1-0 and CL1-5, we found that Shisa3 was highly expressed in the low invasive cells. The effect of Shisa3 on invasion, migration, proliferation, apoptosis, epithelial-mesenchymal transition, and anchorage-independent growth activities in vitro and on tumor growth and metastasis in mice models were examined. The underlying mechanism of Shisa3 was explored by microarray and pathway analysis. Finally, the correlation of Shisa3 expression and clinical outcome was also calculated.
  
  
  RESULTS
  We identified Shisa3 as a novel tumor suppressor, which induces β-catenin degradation resulting in suppression of tumorigenesis and invasion in vitro. Shisa3 decreased the tumor growth in mice with subcutaneous implantation and reduced the number of metastatic nodules in mice with tail vein injection and orthotopic implantation. Shisa3 performs the tumor suppression activity through WNT signaling predicted by microarray analysis. Our data found that Shisa3 accelerates β-catenin degradation and was positively associated with overall survival and progression-free survival of NSCLC.
  
  
  CONCLUSIONS
  Our results reveal that Shisa3 acts as a tumor suppressor by acceleration of β-catenin degradation and provide new insight for cancer prognosis and therapy.
authors.affiliation: 1 Department of Clinical Laboratory Sciences and Medical Biotechnology.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Hong
authors.forename: Bo-Shiun
authors.initials: BS
authors.lastname: Yan
authors.forename: Ching-Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Szu-Hua
authors.initials: SH
authors.lastname: Pan
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Wang
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hung
authors.forename: Shinsheng
authors.initials: S
authors.lastname: Yuan
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Ya-Chien
authors.initials: YC
authors.lastname: Yang
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D046228:Microarray Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D013624:Taiwan; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C514669:Shisa protein, mouse; D051176:beta Catenin
keywords: WNT signaling; metastasis; non–small cell lung cancer; tumor suppressor