title: Knockdown of KRT17 by siRNA induces antitumoral effects on gastric cancer cells.
abstract: BACKGROUND
  Keratin 17 (KRT17) was shown to be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of various cancer types. Our previous studies identified KRT17 as a possible biomarker for gastric cancer by gene microarray, with an elevated expression that occurred early during tumorigenesis and increased during tumor progression. Based on these findings, we aimed to investigate KRT17 biological functions in gastric adenocarcinoma and its possible use as a rational molecular target for anticancer therapy.
  
  
  METHODS
  We used RNA interference-mediated knockdown of KRT17 expression and analyzed the effects on cell proliferation, cell migration, and signal transduction in two gastric cell lines (AGS and NCI-N87) in vitro and on xenograft growth in vivo.
  
  
  RESULTS
  The functional analysis of KRT17 knockdown cell lines showed a decreased cell proliferation (with 42.36% ± 3.2%) and migration ability (with 37.2% ± 6.2%) relative to scrambled siRNA control. The in vivo tumorigenicity on nude mice exhibited a significant decrease in tumor weight with 69.14% in xenografts obtained from AGS cells and 84.43% in xeno-NCI-N87 tumors. The analysis on KRT17 knockdown outcome on intracellular signaling identifies AKT/mTOR as the main affected pathway that sustains proliferation and survival, and also the AMPKα1/CREB pathway that was recently shown to induce organ protection and antiinflammatory response.
  
  
  CONCLUSIONS
  Our results highlight KRT17 as a possible biomarker in gastric cancer promoting tumor growth, motility, and invasion, and suggest that KRT17 can be a valuable molecular target for development of anti-gastric cancer-specific therapies.
authors.affiliation: Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304, Bucharest, Romania. mihaela.chivu@gmail.com.
authors.forename: Mihaela
authors.identifier: http://orcid.org/0000-0001-7512-4700
authors.initials: M
authors.lastname: Chivu-Economescu
authors.affiliation: Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304, Bucharest, Romania.
authors.forename: Denisa L
authors.initials: DL
authors.lastname: Dragu
authors.affiliation: Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304, Bucharest, Romania.|Nicolae Cajal Institute, Titu Maiorescu University, Bucharest, Romania.|Biochemistry-Proteomics Department, Victor Babes National Institute of Pathology, Bucharest, Romania.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Necula
authors.affiliation: Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304, Bucharest, Romania.
authors.forename: Lilia
authors.initials: L
authors.lastname: Matei
authors.affiliation: Biochemistry-Proteomics Department, Victor Babes National Institute of Pathology, Bucharest, Romania.|Cell Biology and Histology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Enciu
authors.affiliation: Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304, Bucharest, Romania.
authors.forename: Coralia
authors.initials: C
authors.lastname: Bleotu
authors.affiliation: Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304, Bucharest, Romania.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Diaconu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D055786:Gene Knockout Techniques; D064593:Heterografts; D006801:Humans; D053537:Keratin-17 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D053537:Keratin-17; D034741:RNA, Small Interfering
keywords: Biomarkers; Gastric cancer; Keratin 17; RNA interference; Targeted therapy