title: Integrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma.
abstract: BACKGROUND
  Integrin-linked kinase (ILK) was first discovered as an integrin β1-subunit binding protein. It localizes at the focal adhesions and is involved in cytoskeleton remodeling. ILK overexpression and its dysregulated signaling cascades have been reported in many human cancers. Aberrant expression of ILK influenced a wide range of signaling pathways and cellular functions. Although ILK has been well characterized in many malignancies, its role in hepatocellular carcinoma (HCC) is still largely unknown.
  
  
  RESULTS
  Quantitative PCR analysis was used to examine ILK mRNA expression in HCC clinical samples. It was shown that ILK was overexpressed in 36.9% (21/57) of HCC tissues when compared to the corresponding non-tumorous livers. The overall ILK expression level was significantly higher in tumorous tissues (P = 0.004), with a significant stepwise increase in expression level along tumor progression from tumor stage I to IV (P = 0.045). ILK knockdown stable clones were established in two HCC cell lines, BEL7402 and HLE, and were subjected to different functional assays. Knockdown of ILK significantly suppressed HCC cell growth, motility and invasion in vitro and inhibited tumorigenicity in vivo. Western blot analysis revealed a reduced phosphorylated-Akt (pAkt) at Serine-473 expression in ILK knockdown stable clones when compared to control clones.
  
  
  CONCLUSIONS
  This study provides evidence about the clinical relevance of ILK in hepatocarcinogenesis. ILK was found to be progressively elevated along HCC progression. Here our findings also provide the first validation about the oncogenic capacity of ILK in vivo by suppressing its expression in HCC cells. The oncogenic role of ILK is implicated to be mediated by Akt pathway.
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chan
authors.forename: Frankie Chi Fat
authors.initials: FC
authors.lastname: Ko
authors.forename: Yin-Shan
authors.initials: YS
authors.lastname: Yeung
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
authors.forename: Judy Wai Ping
authors.initials: JW
authors.lastname: Yam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK