title: Decreased Expression of EHD2 Promotes Tumor Metastasis and Indicates Poor Prognosis in Hepatocellular Carcinoma.
abstract: Metastasis remains the most common cause of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Understanding molecular mechanisms that regulate metastasis process is crucial for improving treatment of hepatocellular carcinoma.
  
  
  
  In this article, we examined whether Eps15 homology domain-containing 2 (EHD2) played a critical role in hepatocellular carcinoma metastasis and explored the possible mechanism.
  
  
  
  EHD2 and E-cadherin expression levels in hepatocellular carcinoma patients were examined using Western blotting and immunohistochemistry. The cell migration and invasion were evaluated by wound-healing assay and trans-well assay. Epithelial-mesenchymal transition was analyzed by immunofluorescence, and the vital markers were detected by Western blotting. The correlation of EHD2 and E-cadherin was confirmed by co-immunoprecipitation.
  
  
  
  EHD2 expression, along with the epithelial marker E-cadherin, was markedly reduced in tumor tissues than in adjacent noncancerous tissues. Moreover, EHD2 was positively correlated with E-cadherin, histological grade, tumor metastasis, and microvascular invasion. Kaplan-Meier survival analysis showed that hepatocellular carcinoma patients with decreased EHD2 expression had shorter overall survival times than those with higher EHD2 expression. Knockdown of EHD2 induced an increase in cell invasion and changes characteristic of epithelial-mesenchymal transition, while overexpression of EHD2 inhibited these processes.
  
  
  
  Molecular data indicated that EHD2 inhibited migration and invasion of hepatocellular carcinoma probably by interacting with E-cadherin and it might be an independent, significant risk factor for survival after curative resection.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Lishuai
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Cui
authors.affiliation: Grade 14, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Grade 14, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Grade 14, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China. Nirunzhou@yeah.net.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; C406446:EHD2 protein, human
keywords: E-cadherin; EHD2; Hepatocellular carcinoma; Metastasis