Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation

Shoki Sato; Toru Nakamura; Toyomasa Katagiri; Takahiro Tsuchikawa; Toshihiro Kushibiki; Kouji Hontani; Mizuna Takahashi; Kazuho Inoko; Hironobu Takano; Hirotake Abe; Shintaro Takeuchi; Masato Ono; Shota Kuwabara; Kazufumi Umemoto; Tomohiro Suzuki; Osamu Sato; Yusuke Nakamura; Satoshi Hirano

doi:10.18632/oncotarget.21939

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation

Shoki Sato, Toru Nakamura _, Toyomasa Katagiri, Takahiro Tsuchikawa, Toshihiro Kushibiki, Kouji Hontani, Mizuna Takahashi, Kazuho Inoko, Hironobu Takano, Hirotake Abe, Shintaro Takeuchi, Masato Ono, Shota Kuwabara, Kazufumi Umemoto, Tomohiro Suzuki, Osamu Sato, Yusuke Nakamura and Satoshi Hirano

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2017; 8:113662-113672. https://doi.org/10.18632/oncotarget.21939

Metrics: PDF 1295 views | HTML 2655 views | ?

Abstract

Shoki Sato1, Toru Nakamura1, Toyomasa Katagiri2, Takahiro Tsuchikawa1, Toshihiro Kushibiki1, Kouji Hontani1, Mizuna Takahashi1, Kazuho Inoko1, Hironobu Takano1, Hirotake Abe1, Shintaro Takeuchi1, Masato Ono1, Shota Kuwabara1, Kazufumi Umemoto1, Tomohiro Suzuki1, Osamu Sato1, Yusuke Nakamura3 and Satoshi Hirano1

1Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

2Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan

3Department of Medicine and Surgery, The University of Chicago, Chicago, IL, USA

Correspondence to:

Toru Nakamura, email: [email protected]

Keywords: C16orf74; pancreatic ductal adenocarcinoma; cell-permeable peptide; molecular target therapy

Received: May 04, 2017 Accepted: July 26, 2017 Published: October 19, 2017

ABSTRACT

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.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 21939

Publication Alerts

Research Papers:

Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation

Abstract