title: TIS21/BTG2 inhibits invadopodia formation by downregulating reactive oxygen species level in MDA-MB-231 cells.
abstract: OBJECTIVE
  Invasion of cancer cells depends on the proteolytic degradation of extracellular matrix regulated by actin-driven membrane protrusions, called invadopodia. However, the mechanisms underlying invadopodia formation in cancer cells remain largely unknown.
  
  
  METHODS
  By employing adenoviral transduction of breast cancer cells with either β-galactosidase (Ad-LacZ) or TIS21(/BTG2/Pc3) (Ad-TIS21) gene, the regulation of invadopodia formation was investigated. Invasion activity was examined by invadopodia assay and Matrigel assay. Intracellular reactive oxygen species (ROS) was monitored by FACS-based analysis.
  
  
  RESULTS
  Here, we observed that TIS21 suppressed invadopodia formation as well as invasion activity along with F-actin remodeling. The inhibition of TIS21-mediated invadopodia formation was accompanied with attenuation of ROS generation in the TIS21 expressers, indicating that TIS21-mediated inhibition of ROS plays a critical role for invadopodia formation by regulating actin-associated protein remodeling. This was further confirmed in the TIS21(-/-)MEF cells.
  
  
  CONCLUSIONS
  This is the first report to provide insight into invasion signals regulated by tumor suppressor, TIS21(/BTG2/Pc3) gene, in the intractable breast cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon, 443-721, Korea.
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Choi
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D017382:Reactive Oxygen Species / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D017874:Immediate-Early Proteins; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human
references.citation: Cancer Res. 2007 Feb 15;67(4):1618-25
references.pmid: 17308102
references.citation: Trends Cell Biol. 2003 Jul;13(7):376-85
references.pmid: 12837608
references.citation: Nat Rev Mol Cell Biol. 2004 Aug;5(8):647-57
references.pmid: 15366708
references.citation: Cancer Res. 2006 Jul 15;66(14):7075-82
references.pmid: 16849553
references.citation: Nature. 2002 Jan 31;415(6871):530-6
references.pmid: 11823860
references.citation: IUBMB Life. 2000 Oct-Nov;50(4-5):291-9
references.pmid: 11327323
references.citation: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3353-7
references.pmid: 1849653
references.citation: Cancer Cell. 2011 Mar 8;19(3):372-86
references.pmid: 21397860
references.citation: Cancer Res. 2008 Jul 1;68(13):5405-13
references.pmid: 18593943
references.citation: J Cancer Res Clin Oncol. 2006 Jul;132(7):417-26
references.pmid: 16456675
references.citation: Cancer Res. 2009 Nov 15;69(22):8594-602
references.pmid: 19887621
references.citation: J Cancer Res Clin Oncol. 1995;121(5):279-84
references.pmid: 7768965
references.citation: Cancer Lett. 2008 Aug 18;267(1):125-32
references.pmid: 18433991
references.citation: Nat Genet. 1996 Dec;14(4):482-6
references.pmid: 8944033
references.citation: J Biol Chem. 1991 Aug 5;266(22):14511-8
references.pmid: 1713584
references.citation: Oncogene. 2011 Jul 7;30(27):3084-95
references.pmid: 21339742
references.citation: Cancer Res. 2006 Mar 15;66(6):3034-43
references.pmid: 16540652
references.citation: J Cell Biol. 2005 Jan 31;168(3):441-52
references.pmid: 15684033
references.citation: Mol Cell Biol. 2004 Dec;24(23):10256-62
references.pmid: 15542835
references.citation: Carcinogenesis. 2001 Aug;22(8):1271-9
references.pmid: 11470758
references.citation: Cancer Res. 2004 Mar 1;64(5):1632-8
references.pmid: 14996721
references.citation: J Cell Biol. 2003 Jun 9;161(5):933-44
references.pmid: 12796479
references.citation: Curr Opin Cell Biol. 2005 Oct;17(5):559-64
references.pmid: 16098726
references.citation: J Clin Neurosci. 2008 Jul;15(7):725-37
references.pmid: 18468901
references.citation: J Neurosci. 2012 Oct 31;32(44):15547-64
references.pmid: 23115191
references.citation: Cancer Res. 2007 May 1;67(9):4227-35
references.pmid: 17483334
references.citation: Clin Cancer Res. 1998 Feb;4(2):507-15
references.pmid: 9516943
references.citation: Sci Signal. 2009 Sep 15;2(88):ra53
references.pmid: 19755709
references.citation: Nat Rev Cancer. 2002 Aug;2(8):563-72
references.pmid: 12154349
references.citation: FEBS Lett. 2001 May 25;497(2-3):67-72
references.pmid: 11377414
references.citation: Cancer Res. 2011 Mar 1;71(5):1730-41
references.pmid: 21257711
references.citation: Tissue Cell. 2002 Feb;34(1):28-32
references.pmid: 11989967
references.citation: Hepatology. 2008 May;47(5):1533-43
references.pmid: 18393292