title: Survivin inhibition by an interacting recombinant peptide, derived from the human ferritin heavy chain, impedes tumor cell growth.
abstract: BACKGROUND
  Proteins involved in the aberrant regulation of signaling pathways and their downstream effectors are promising targets for cancer therapy. Survivin is an anti-apoptotic and cell cycle-promoting protein, which is consistently overexpressed in cancer cells. In normal cells, its expression is tightly controlled by signaling pathways and their associated transcriptional activators and repressors. In cancer cells, its expression is enhanced as a consequence of oncogenic signaling. We investigated the potential of a novel, peptide-based survivin inhibitor in breast cancer (SK-BR-3, MDA-MB-468) and glioblastoma (Tu9648) cells. These cells express high levels of survivin.
  
  
  METHODS
  We downregulated survivin expression in tumor cells with a lentiviral gene transfer vector encoding a specific shRNA and a recombinant fusion protein, rSip, comprising the FTH1-derived survivin interaction domain, the human thioredoxin and a protein transduction domain.
  
  
  RESULTS
  Downregulation of survivin expression decreased the growth and viability of tumor cells in culture and reduced growth of the cancer cells upon transplantation into immunodeficient mice. rSip selectively targets the anti-apoptotic function of survivin and causes tumor cell death. Non-transformed NIH/3T3 and MCF10A cells remain unaffected.
  
  
  CONCLUSIONS
  rSip provides a lead structure for the development of drugs targeting the tumor cell "addiction protein" survivin.
authors.affiliation: Georg-Speyer-Haus, Institute for Biomedical Research, Paul Ehrlich Str. 42-44, 60596, Frankfurt am Main, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weiss
authors.forename: Boris
authors.initials: B
authors.lastname: Brill
authors.forename: Corina
authors.initials: C
authors.lastname: Borghouts
authors.forename: Natalia
authors.initials: N
authors.lastname: Delis
authors.forename: Laura
authors.initials: L
authors.lastname: Mack
authors.forename: Bernd
authors.initials: B
authors.lastname: Groner
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010088:Oxidoreductases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D015398:Signal Transduction / Q000235:genetics; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D005293:Ferritins; C454461:FTH1 protein, human; D010088:Oxidoreductases