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Title
  • en Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation
Creator
    • en Sato, Shoki
    • en Katagiri, Toyomasa
    • en Kushibiki, Toshihiro
    • en Hontani, Kouji
    • en Takahashi, Mizuna
    • en Inoko, Kazuho
    • en Takano, Hironobu
    • en Abe, Hirotake
    • en Takeuchi, Shintaro
    • en Ono, Masato
    • en Kuwabara, Shota
    • en Umemoto, Kazufumi
    • en Suzuki, Tomohiro
    • en Sato, Osamu
    • en Nakamura, Yusuke
Accessrights open access
Rights
Subject
  • Other en C16orf74
  • Other en pancreatic ductal adenocarcinoma
  • Other en cell-permeable peptide
  • Other en molecular target therapy
  • NDC 490
Description
  • Abstract en Background: Chromosome 16 open reading frame 74 (C16orf74) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo. Method: TheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects. Result: DN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR. Conclusion: The cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.
Publisher en Impact Journals
Date
    Issued2017-12-26
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/68595
Relation
  • isIdenticalTo DOI https://doi.org/10.18632/oncotarget.21939
Journal
    • PISSN 1949-2553
      • en Oncotarget
      • Volume Number8 Issue Number69 Page Start113662 Page End113672
File
Oaidate 2023-07-26