title: Silencing Met receptor tyrosine kinase signaling decreased oral tumor growth and increased survival of nude mice.
abstract: OBJECTIVE
  The hepatocyte growth factor receptor (Met) is frequently overexpressed in Head and Neck Squamous Cell Carcinoma (HNSCC), correlating positively with high-grade tumors and shortened patient survival. As such, Met may represent an important therapeutic target. The purpose of this study was to explore the role of Met signaling for HNSCC growth and locoregional dissemination.
  
  
  METHODS
  Using a lentiviral system for RNA interference, we knocked down Met in established HNSCC cell lines that express high levels of the endogenous receptor. The effect of Met silencing on in vitro proliferation, cell survival and migration was examined using western analysis, immunohistochemistry and live cell imaging. In vivo tumor growth, dissemination and mouse survival was assessed using an orthotopic tongue mouse model for HNSCC.
  
  
  RESULTS
  We show that Met knockdown (1) impaired activation of downstream MAPK signaling; (2) reduced cell viability and anchorage independent growth; (3) abrogated HGF-induced cell motility on laminin; (4) reduced in vivo tumor growth by increased cell apoptosis; (5) caused reduced incidence of tumor dissemination to regional lymph nodes and (6) increased the survival of nude mice with orthotopic xenografts.
  
  
  CONCLUSIONS
  Met signaling is important for HNSCC growth and locoregional dissemination in vivo and that targeting Met may be an important strategy for therapy.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: X
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: K S
authors.initials: KS
authors.lastname: Hill
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: I
authors.initials: I
authors.lastname: Gaziova
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States; Department of Sealy Center for Cancer Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: S K
authors.initials: SK
authors.lastname: Sastry
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States; Department of Sealy Center for Cancer Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: S
authors.initials: S
authors.lastname: Qui
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: P
authors.initials: P
authors.lastname: Szaniszlo
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: S
authors.initials: S
authors.lastname: Fennewald
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States; Department of Sealy Center for Cancer Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States.
authors.forename: V A
authors.initials: VA
authors.lastname: Resto
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States; Department of Sealy Center for Cancer Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, United States. Electronic address: lisa.elferink@utmb.edu.
authors.forename: L A
authors.initials: LA
authors.lastname: Elferink
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D010879:Piperazines / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014062:Tongue Neoplasms / Q000378:metabolism*
chemical_list: C478479:((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide); D007211:Indoles; D010879:Piperazines; D034741:RNA, Small Interfering; D013449:Sulfonamides; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: HGF receptor; Head and neck squamous cell carcinoma; MET; Oral cancer; Tumorigenesis