Related Experiment Video
Updated: Feb 23, 2026

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
Overexpression of C16orf74 is involved in aggressive pancreatic cancers
Toru Nakamura1,2, Toyomasa Katagiri1,3, Shoki Sato2
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
Abstract:
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 sapienschromosome 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.
Insights
Chromosome 16 open reading frame 74 (C16orf74) is upregulated in pancreatic ductal adenocarcinoma (PDAC). Targeting C16orf74 may offer a new therapeutic strategy for PDAC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) outcomes remain poor due to limited targeted therapies.
- Identifying novel therapeutic targets is crucial for improving PDAC treatment.
Purpose of the Study:
- To identify a novel therapeutic target for PDAC.
- To investigate the role of Chromosome 16 open reading frame 74 (C16orf74) in PDAC.
Main Methods:
- Genome-wide analysis to identify upregulated genes in PDAC.
- Immunohistochemical analysis to assess C16orf74 protein expression and prognostic value.
- Small hairpin RNA (shRNA) mediated knockdown of C16orf74 in PDAC cell lines.
- Ectopic overexpression of C16orf74 in non-PDAC cell lines.
- Interaction studies between C16orf74 and protein phosphatase 3 catalytic subunit alpha (PPP3CA).
Main Results:
- C16orf74 was significantly upregulated in the majority of PDAC samples.
- Overexpression of C16orf74 correlated with poorer prognosis in PDAC patients.
- C16orf74 knockdown inhibited PDAC cell growth, while its overexpression promoted cell growth and invasion.
- C16orf74 interacts with PPP3CA, and this interaction is critical for PDAC cell invasion.
Conclusions:
- C16orf74 plays a critical role in PDAC invasion and proliferation.
- C16orf74 represents a promising therapeutic target for PDAC treatment.
Related Concept Videos
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Induced Pluripotent Stem Cells
Somatic...
The Ras Gene
Ras is a...

