Research Papers:

Overexpression of C16orf74 is involved in aggressive pancreatic cancers

Toru Nakamura, Toyomasa Katagiri, Shoki Sato, Toshihiro Kushibiki, Koji Hontani, Takahiro Tsuchikawa, Satoshi Hirano and Yusuke Nakamura _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:50460-50475. https://doi.org/10.18632/oncotarget.10912

Metrics: PDF 2794 views  |   HTML 3206 views  |   ?  


Toru Nakamura1,2, Toyomasa Katagiri1,3, Shoki Sato2, Toshihiro Kushibiki2, Koji Hontani2, Takahiro Tsuchikawa2, Satoshi Hirano2 and Yusuke Nakamura1,4

1 Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan

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

3 Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Kuramoto-cho, Tokushima, Japan

4 Department of Medicine and Surgery, The University of Chicago, Chicago, Illinois, USA

Correspondence to:

Yusuke Nakamura, email:

Keywords: pancreatic cancer, novel gene, molecular target

Received: April 21, 2016 Accepted: June 13, 2016 Published: July 28, 2016


Clinical outcome of pancreatic ductal adenocarcinoma (PDAC) has not been improved in the last three decades due to the lack of effective molecular-targeted drugs. To identify a novel therapeutic target for PDAC, we have performed genome-wide anamysis and found that Homo sapiens chromosome 16 open reading frame 74 (C16orf74) was up-regulated in the vast majority of PDAC. Overexpression of C16orf74protein detected by immunohistochemical analysis was an independent prognostic factor for patients with PDAC. The knockdown of endogenous C16orf74 expression in the PDAC cell lines KLM-1 and PK-59 by vector-based small hairpin-RNA (shRNA) drastically attenuated the growth of those cells, whereas ectopic C16orf74 overexpression in HEK293T and NIH3T3 cells promoted cell growth and invasion, respectively. More importantly, the endogenous threonine 44 (T44)-phosphorylated form of C16orf74 interacted with the protein phosphatase 3 catalytic subunit alpha (PPP3CA) via the PDIIIT sequence in the PPP3CA-binding motif within the middle portion of C16orf74 in PDAC cells. The overexpression of mutants of C16orf74 lacking the PDIIIT sequence or T44 phosphorylation resulted in the suppression of invasive activity compared with wild-type C16orf74, indicating that their interaction should be indispensable for PDAC cell invasion. These results suggest that C16orf74 plays an important role for PDAC invasion and proliferation, and is a promising target for a specific treatment for patients with PDAC.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 10912