title: SIRT1 enhances matrix metalloproteinase-2 expression and tumor cell invasion in prostate cancer cells.
abstract: BACKGROUND
  Matrix metalloproteinase-2 (MMP2) has been shown to play an important role in cancer cell invasion and the expression of MMP2 is associated with the poor prognosis of prostate cancer; however, the mechanism of MMP2 expression is largely unknown. SIRT1 is a nicotinamide adenine dinucleotide-dependent histone deacetylase (class III HDAC) that has recently been shown to have implications in regulating cancer cell growth and apoptosis. The purpose of this study is to determine the role of SIRT1 in regulating MMP2 expression and tumor invasion in prostate cancer cells.
  
  
  METHODS
  The interfering RNAi was used to knockdown SIRT1 from prostate cancer cells. Immunoblots, RT-PCR, zymographic assays, co-immunoprecipitation, analysis and transwell assays were used to examine the effects of SIRT1 silencing on MMP2 expression and activity, on SIRT1 and MMP2 interaction, and on prostate cancer cell invasion. The immuno-histochemical assay was performed to study SIRT1 expression in prostate cancer tissues.
  
  
  RESULTS
  We show that SIRT1 associates and deacetylates MMP2 and SIRT1 regulates MMP2 expression by controlling MMP2 protein stability through the proteosomal pathway. Thus, we demonstrated a novel mechanism in that MMP2 expression can be regulated at the posttranslational level by SIRT1. Furthermore, we determined that SIRT1 inhibition reduced prostate cancer cell invasion and SIRT1 is highly expressed in advanced prostate cancer tissues.
  
  
  CONCLUSIONS
  SIRT1 is an important regulator of MMP2 expression, activity, and prostate cancer cell invasion. Overexpressed SIRT1 in advanced prostate cancer may play an important role in prostate cancer progression.
authors.affiliation: Cancer Research Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Jenna D
authors.initials: JD
authors.lastname: Lovaas
authors.forename: Lijia
authors.initials: L
authors.lastname: Zhu
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Chiao
authors.forename: Vanessa
authors.initials: V
authors.lastname: Byles
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faller
authors.forename: Yan
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025801:Ubiquitin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D046988:Proteasome Endopeptidase Complex; C447939:SIRT1 protein, human; D056564:Sirtuin 1