<<<<< << <<< /> or progression, suggesting a role for this protein as or progression, suggesting a role for this protein asor progression, suggesting a role for this protein as or progression, suggesting a role for this protein as a bor progression, suggesting a role for this protein as a biomor progression, suggesting a role for this protein asor progression, suggesting a role for this protein as a bor progression, suggesting a role for this protein as a bioor progression, suggesting a role for this protein as a or progression, suggesting a role for this protein as a biomor progression, suggesting a role for this protein as a bioor progression, suggesting a role for this protein as a bior progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive SCCs. [Cancer Res 2008;68(10):3959?69]" /> iate SCC invasion via degradation of the extracellular matrixiate SCC invasion via degradation of the extracellular matriiate SCC invasion via degradation of the extracellular matriiate SCC invasion via degradation of the extracellular matrix. Using SCC cells transfected with empty vector or Rap1GAP, cell invasion and MMP secretion were determined by Matrigel assays and gelatin iate SCC invasion via degradation of the extracellular matrix. Using SCC cells transfected with empty vector or Rap1GAP, cell invasion and MMP secretion were determined by Matrigel assays and gelatin zymography, respectively. Rap1GAP up-regulated transcription and secretion of MMP2 and MMP9, as assayed by quantitative reverse transcription-PCR and zymography. Furthermore, chemical and RNA interference bdings suggest that Rap1GAP acts as a tumor suppressor protein in SCC by delaying the G<sub>1</sub>-S transition of the cell cycle. However, cells transfected with Rap1GAP exhibit a more invasive phenotype than corresponding vector-transfected control cells. MMP2 and MMP9 are enzymes that mediate SCC invasion via degradation of the extracellular matrix. Using SCC cells transfected with empty vector or Rap1GAP, cell invasion and MMP secretion were determined by Matrigel assays and gelatin zymography, respectively. Rap1GAP up-regulated transcription and secretion of MMP2 and MMP9, as assayed by quantitative reverse transcription-PCR and zymography. Furthermore, chemical and RNA interference blockade of MMP2/MMP9 inhibited invasion by Rap1GAP-transfected cells. Immunohistochemical staining of a human oropharyngeal SCC tissue microarray showed that Rap1GAP and MMP9 expression and staining intensity are correlated (<i>P</i> &lt; 0.0001) and that, in early N-stage lesions of SCC, high MMP9 is prognostic of poor disease-specific survival (<i>P</i> &lt; 0.05). Furthermore, Rap1GAP staining is correlated with MMP2 (<i>P</i> &lt; 0.03). MMP2 in combination with N stage has a prognostic effect on time to indication of surgery at primary site. MMP2 intensity is also positively correlated with T stage (<i>P</i> &lt; 0.015). In conclusion, Rap1GAP inhibits tumor growth but induces MMP2- and MMP9-mediated SCC invasion and tumor progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive SCCs. [Cancer Res 2008;68(10):3959?69]</p>" /> dings suggest that Rap1GAP acts as a tumor suppressor protein in dings suggest that Rap1GAP acts as a tumor suppressor protein in SCC by delaying the Gdings suggest that Rap1GAP acts as a tumor suppressor protein idings suggest that Rap1GAP acts as a tumor suppressor protdings suggest that Rap1GAP acts as a tumor suppredings suggest that Rap1GAP acts as a tumor suppressor protein in SCC ls.org/content/68/10/3959" /> ls.org/content/68/10/3959" /> at Clin Pract Oncol;citation_pages=156;citation_volume=4;citation_year=2007;citation_pmid=17327856;citation_doi=10.1038/ncponc0750" /> ssue=1;citation_issn=0031-9333;citation_pmid=11152757" /> ear=2002;citation_issue=5558;citation_issn=0036-8075;citation_pmid=11847339;citation_doi=10.1126/science.1067549" /> _journal_abbrev=Cancer Res.;citation_title=Tumor Cell Surface-associated Binding Site for the Mr 72,000 Type IV Collagenase;citation_pages=5845-5848;citation_volume=52;citation_year=1992;citation_issue=20;citation_issn=0008-5472;citation_pmid=1394213" /> aryngeal cancer.;citation_pages=MT42-MT47;citation_volume=9;citation_year=2003;citation_issue=3;citation_pmid=12640351" /> Is Expressed by Advanced Stage Melanoma Cells: Suppression by Somatic Cell Hybridization with Early Stage Melanoma Cells;citation_pages=4174-4181;citation_volume=55;citation_year=1995;citation_issue=18;citation_issn=0008-5472;citation_pmid=7664294" /> zation of human Rap1GAP.;citation_pages=752-754;citation_volume=60;citation_year=2004;citation_issue=Pt 4;citation_pmid=15039575;citation_doi=10.1107/S0907444904002392" /> reference" content="citation_title=Annals of Otology, Rhinology & Laryngology;citation_journal_abbrev=Ann Otol Rhinol Laryngol;citation_title=Expression of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Head and Neck Squamous Cell Carcinoma;citation_pages=271-278;citation_volume=106;citation_year=1997;citation_issue=4;creference" content="citation_title=Annals of Otology, Rhinology & Laryngology;citation_journal_abbrev=Ann Otol Rhinol Laryngol;citation_title=Expression of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Head and Neck Squamous Cell Carcinoma;citation_pages=271-278;citation_volume=106;citation_year=1997;citation_issue=4;citation_issn=0003-4894;citation_pmid=9109715;citation_doi=10.1177/000348949710600402" /> 9(03)00172-9" /> y;citation_journal_abbrev=Eur J Cell Biol;citation_title=Tissue inhibitors of metalloproteinases: structure, regulation and biological functions.;citation_pages=111-122;citaty;citation_journal_abbrev=Eur J Cell Biol;citation_title=Tissue inhibitors of metalloproteinases: structure, regulation and biological functions.;citation_pages=111-122;citation_volumy;citation_jouryyyyy;y;citation_journal_abbrev=Eur J Cell Biol;citation_title=Tissue inhibitors of metalloproteinases: structure, regulation and biological functions.;citation_pages=111-122;citation_volume=74;citation_year=1997;citation_issue=2;citation_pmid=9352216" /> ..a.aacrjournals.org/sites/default/files/advagg_css/css__vP96nkAt3EeLU62QRdHXKZuS9tqQ1EMDJC_PSKd7hEk__ytmGDfxpC-NYUARFvuXXsi8j4rHj-bHcrpQ6NGYbpUE__jOYEfIB0OEniODn0QXr3j-SWWXrGgnqWe0fls04qgok.css" media="all" /> NNN NN N NN tt )","x)","xsmall":"all and (min-width: 380px)","narrow":"all and (min-width: 768px) and (min-device-width: 768px)","xsmall)","xsmall":"all and (min-width: 380px)","narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (mi)","xsmall":"all and (min-wi)","xsmall