SynthesisLaboratory investigation; a journal of technical methods and pathology2014
Loss of HNF6 expression correlates with human pancreatic cancer progression.
Synthesis in Laboratory investigation; a journal of technical methods and pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.Journal of cancer research and clinical oncology · 2018Pooled it
- Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation.Developmental cell · 2026Article
- Overexpression of ONECUT1 suppresses hepatoblastoma progression via modulating tumor cell growth and tumor microenvironment.Cell & bioscience · 2026Article
- Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Regulation of the Pancreatic Exocrine Differentiation Program and Morphogenesis by Onecut 1/Hnf6.Cellular and molecular gastroenterology and hepatology · 2019Article
- Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors impacts postnatal islet maturation and adaptability.American journal of physiology. Endocrinology and metabolism · 2018Article
- Transcriptional variations in the wider peritumoral tissue environment of pancreatic cancer.International journal of cancer · 2018Article
- Development of bioluminescent chick chorioallantoic membrane (CAM) models for primary pancreatic cancer cells: a platform for drug testing.Scientific reports · 2017Article
- Deguelin inhibits proliferation and migration of human pancreatic cancer cellsOncology letters · 2016Article
- Threshold-Dependent Cooperativity of Pdx1 and Oc1 in Pancreatic Progenitors Establishes Competency for Endocrine Differentiation and β-Cell Function.Cell reports · 2016Article
- Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122.Journal of cancer research and clinical oncology · 2016Article
- Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation.Neoplasia (New York, N.Y.) · 2016Article
- Onecut transcription factors in development and disease.Trends in developmental biology · 2016Article
- The School for Science and Math at Vanderbilt: An Innovative Research-Based Program for High School Students.CBE life sciences education · 2014Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Normal pancreatic epithelium progresses through various stages of pancreatic intraepithelial neoplasms (PanINs) in the development of pancreatic ductal adenocarcinoma (PDAC). Transcriptional regulation of this progression is poorly understood. In mouse, the hepatic nuclear factor 6 (Hnf6) transcription factor is expressed in ductal cells and at lower levels in acinar cells of the adult pancreas, but not in mature endocrine cells. Hnf6 is critical for terminal differentiation of the ductal epithelium during embryonic development and for pancreatic endocrine cell specification. We previously showed that, in mice, loss of Hnf6 from the pancreatic epithelium during organogenesis results in increased duct proliferation and altered duct architecture, increased periductal fibrosis and acinar-to-ductal metaplasia. Here we show that decreased expression of HNF6 is strongly correlated with increased severity of PanIN lesions in samples of human pancreata and is absent from >90% of PDAC. Mouse models in which cancer progression can be analyzed from the earliest stages that are seldom accessible in humans support a role for Hnf6 loss in progression from early- to late-stage PanIN and PDAC. In addition, gene expression analyses of human pancreatic cancer reveal decreased expression of HNF6 and its direct and indirect target genes compared with normal tissue and upregulation of genes that act in opposition to HNF6 and its targets. The negative correlation between HNF6 expression and pancreatic cancer progression suggests that HNF6 maintains pancreatic epithelial homeostasis in humans, and that its loss contributes to the progression from PanIN to ductal adenocarcinoma. Insight on the role of HNF6 in pancreatic cancer development could lead to its use as a biomarker for early detection and prognosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.