title: NEDD4 Depletion Inhibits Hepatocellular Carcinoma Growth via Targeting PTEN.
abstract: OBJECTIVE
  Neural precursor cell-expressed developmentally down-regulated gene 4 (NEDD4) plays an important role in tumor cell growth, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study is to establish NEDD4 as a prognostic biomarker by which the survival of HCC patients can be predicted and to reveal the role of NEDD4 in hepatocellular carcinoma cell growth.
  
  
  METHODS
  The expression of NEDD4 in 219 HCC specimens was assessed by immunohistochemistry. Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses. The roles of NEDD4 in hepatocellular carcinoma cell proliferation and invasion were determined.
  
  
  RESULTS
  The patients with low NEDD4 expression tumors had an average cumulative survival of 64.9 ± 6.5 months during follow-up while the patients with high NEDD4 expression tumors had an average cumulative survival of 20.3 ± 15.8 months. NEDD4 silencing inhibited Huh7 cell proliferation and altered cell cytoskeletal assembly, and NEDD4 depletion furthermore seemed to suppress cell migration and invasion. A possible molecular mechanism for the observed effects might be that NEDD4 silence led to an increase in PTEN (phosphatase and tensin homologue) expression, which in turn resulted in the inactivation of STAT3, AKT, and ERK1/2.
  
  
  CONCLUSIONS
  Our findings indicate that NEDD4 may participate in the HCC progression and may therefore be a potential target for HCC therapy.
authors.affiliation: Department of Infection Diseases, Changzheng Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hang
authors.forename: Shanbang
authors.initials: S
authors.lastname: Zhu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Di
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Wu
authors.forename: Kaijian
authors.initials: K
authors.lastname: Chu
authors.forename: Junxue
authors.initials: J
authors.lastname: Wang
authors.forename: Haiguang
authors.initials: H
authors.lastname: Xin
authors.forename: Guanzhen
authors.initials: G
authors.lastname: Yu
authors.forename: Haoran
authors.initials: H
authors.lastname: Peng
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Miao
authors.forename: Wensheng
authors.initials: W
authors.lastname: Xu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human