title: Integrin-linked kinase silencing induces a S/G2/M phases cell cycle slowing and modulates metastasis-related genes in SGC7901 human gastric carcinoma cells.
abstract: OBJECTIVE
  Integrin-linked kinase has been implicated in metastasis of human tumors. Recent studies have also shown that the down-regulation of integrin-linked kinase has anti-tumor potential by inhibiting the metastatic potential of several types of cultured human cancer cells. However, the mechanism by which integrin-linked kinase regulates metastasis in human gastric carcinoma is not fully clear. We investigated the effect of integrin-linked kinase deletion on metastasis-associated markers in human gastric carcinoma SGC-7901 cell lines.
  
  
  METHODS
  We generated cell lines depleted for integrin-linked kinase. Cell adhesion and invasion were measured by the MTS assay and transwell assay. The cell cycle was measured by flow cytometry. Expression of metastasis-related genes was assessed by reporter assay, quantitative RT-PCR and western blotting.
  
  
  RESULTS
  Our data showed an inhibitory effect on cell adhesion and invasion after silencing of integrin-linked kinase. The cell cycle was slowed in S/G2/M phases. Metastasis-related genes E-cadherin, MMP-2/9 and cystatin B, as well as the signaling molecules p-Akt, NF-κB, and AP-1 activation, were also modulated. Our results indicate that integrin-linked kinase plays an important role in metastasis of human gastric carcinoma cells.
  
  
  CONCLUSIONS
  Down-regulation of integrin-linked kinase resulted in the impairment of the metastatic potential of gastric tumor cells by regulating metastasis-related gene expression, by inhibiting the Akt pathway as well as the activity of transcription factors. Integrin-linked kinase could be used as a potential therapeutic target.
authors.affiliation: Department of Oncology, Provincial Hospital affiliated to Shandong University, Jinan, China. songwei_sd@yahoo.com.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Chunming
authors.initials: C
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
mesh_terms: D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005434:Flow Cytometry; D016195:G2 Phase / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D000099200:Scaffold Protein ILK
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000099200:Scaffold Protein ILK