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Updated: Jul 9, 2026
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Published on: May 26, 2023
Loss of ONECUT1 expression in human pancreatic cancer cells
Xiaohua Jiang1, Weiwei Zhang, Hany Kayed
1Department of Surgery, Technische Universität München, 81675 Munich, Germany.
Abstract:
ONECUT1 (HNF-6) is the prototype of a new class of homeodomain transcription factors, that controls the development of pancreatic ducts during mouse development. In the present study, the role of ONECUT1 and its targeted genes TCF2, PKHD1 and CYS1 was analyzed in human pancreatic ductal adenocarcinoma (PDAC). mRNA levels of ONECUT1, TCF2, PKHD1 and CYS1 were measured in pancreatic tissues and pancreatic cancer cell lines by quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR). Protein expression of ONECUT1 and TCF2 was assessed in pancreatic tissues by immunohistochemistry. ONECUT1 was transfected into Panc-1 and T3M4 pancreatic cancer cells and its effects on anchorage-dependent and -independent growth as well as invasion and adhesion were analyzed. Median mRNA levels of ONECUT1, TCF2, PKHD1 and CYS1 were 7.7-, 2.0-, 5.7- and 3.8-fold higher in normal tissues than in PDAC tissues. ONECUT1 protein was expressed in normal acinar and ductal cells, but neither in the cancer cells of PDAC tissues nor in 7 of 8 cultured pancreatic cancer cell lines. There was a significant positive correlation between ONECUT1 and TCF2, CYS1, and PKHD1 mRNA levels in PDAC tissues. Transfection of ONECUT1 into pancreatic cancer cells resulted in up-regulation of the target gene TCF2, a reduction in invasiveness, but no change in adhesion or growth. In conclusion, ONECUT1 expression is lost in pancreatic cancer cells, suggesting a tumor suppressor function in this malignancy.
Insights
ONECUT1 (HNF-6) is often lost in pancreatic cancer, suggesting it may act as a tumor suppressor. This study investigated its role and that of its target genes in pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- ONECUT1 (HNF-6) is a homeodomain transcription factor crucial for pancreatic duct development in mice.
- Its role in human pancreatic ductal adenocarcinoma (PDAC) and its target genes (TCF2, PKHD1, CYS1) remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of ONECUT1 and its target genes in human PDAC.
- To determine if ONECUT1 has a tumor suppressor role in pancreatic cancer.
Main Methods:
- Quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) to measure mRNA levels of ONECUT1, TCF2, PKHD1, and CYS1 in tissues and cell lines.
- Immunohistochemistry to assess ONECUT1 and TCF2 protein expression in tissues.
- In vitro functional assays (transfection) to analyze the effects of ONECUT1 on pancreatic cancer cell behavior (growth, invasion, adhesion).
Main Results:
- Median mRNA levels of ONECUT1, TCF2, PKHD1, and CYS1 were significantly lower in PDAC tissues compared to normal tissues.
- ONECUT1 protein was expressed in normal pancreatic cells but absent in PDAC tissues and most cancer cell lines.
- ONECUT1 transfection into cancer cells reduced invasiveness and upregulated TCF2, but did not affect growth or adhesion.
- A positive correlation was observed between ONECUT1 and its target gene mRNA levels in PDAC tissues.
Conclusions:
- ONECUT1 expression is frequently lost in human pancreatic ductal adenocarcinoma.
- The loss of ONECUT1 in PDAC suggests a tumor suppressor role.
- ONECUT1 may regulate cancer cell invasiveness through its target gene TCF2.
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