title: The role of ZNRF2 in the growth of non-small cell lung cancer.
abstract: ZNRF2 belongs to ubiquitin ligases of the RING superfamily, and has been recently shown to be regulated by Akt to interact with a Mechanistic target of rapamycin (mTor). Nevertheless, a role of ZNRF2 in tumorigenesis, especially in non-small cell lung cancer (NSCLC), is unknown. Here, we assessed ZNRF2 expression in NSCLC.
  
  
  
  We examined ZNRF2 levels by Western blot using NSCLC specimens, compared to the paired non-tumor controls. We also examined the effects of ZNRF2 on cell growth and cell survival in the presence of fluorouracil.
  
  
  
  We detected significant higher levels of ZNRF2 and mTor in NSCLC tissues, compared to the paired non-tumor controls. Moreover, ZNRF2 and mTor levels strongly correlated in NSCLC tissues. High ZNRF2 levels were correlated with poor prognosis of the NSCLC patients. In vitro, overexpression of ZNRF2 increased NSCLC cell growth and suppressed apoptotic cell death in the presence of Fluorouracil, while depletion of ZNRF2 decreased NSCLC cell growth and increased apoptotic cell death in the presence of fluorouracil. ZNRF2 appeared to augment mTor and its downstream targets CyclinD1 and CDK in NSCLC cells.
  
  
  
  ZNRF2 may be a promising target for treating NSCLC.
authors: Department of Thoracic Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. wzzxf308@yeah.net.
authors: X-F
authors: XF
authors: Zhang
authors: Z-Q
authors: ZQ
authors: Guo
authors: C-C
authors: CC
authors: Zhao
authors: C-Y
authors: CY
authors: Xu
authors: M
authors: M
authors: Han
authors: C
authors: C
authors: Li
authors: Z
authors: Z
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D000970:Antineoplastic Agents; D044767:Ubiquitin-Protein Ligases; C580704:ZNRF2 protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005472:Fluorouracil