title: Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K.
abstract: BACKGROUND
  Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics, although only coronin 3 has been shown to be related to cancer cell migration. In glioblastoma cells, the knockdown of coronin 3 inhibits cell proliferation and invasion. Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma. In this paper, we analyze the migration, invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3, and explore the mechanism of coronin 3 in the process of gastric cancer metastasis.
  
  
  RESULTS
  The expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M, which we established in our laboratory. We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues, and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis. Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines. Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells. In contrast, up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells. In addition, knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells. The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3, and the results suggested that, following the knockdown of coronin 3, the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K.
  
  
  CONCLUSIONS
  Coronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells, including their migration and invasion.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Ren
authors.forename: Qifei
authors.initials: Q
authors.lastname: Tian
authors.forename: Yanxin
authors.initials: Y
authors.lastname: An
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Yulong
authors.initials: Y
authors.lastname: Shang
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D056657:Cathepsin K / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D021381:Protein Transport; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D008840:Microfilament Proteins; C072061:coronin proteins; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9