The prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis
Open accessAbstract
Pancreatic exocrine cell plasticity can be observed during development, pancreatitis with subsequent regeneration, and also transformation. For example, acinar–ductal metaplasia (ADM) occurs during acute pancreatitis and might be viewed as a prelude to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) development. To elucidate regulatory processes that overlap ductal development, ADM, and the progression of normal cells to PanIN lesions, we undertook a systematic approach to identify the Prrx1 paired homeodomain Prrx1 transcriptional factor as a highly regulated gene in these processes. Prrx1 annotates a subset of pancreatic ductal epithelial cells in Prrx1creER T2 -IRES-GFP mice. Furthermore, sorted Prrx1 + cells have the capacity to self-renew and expand during chronic pancreatitis. The two isoforms, Prrx1a and Prrx1b, regulate migration and invasion, respectively, in pancreatic cancer cells. In addition, Prrx1b is enriched in circulating pancreatic cells ( Pdx1cre;LSL-Kras G12D/+ ;p53 fl/+ ;R26YFP ). Intriguingly, the Prrx1b isoform, which is also induced in ADM, binds the Sox9 promoter and positively regulates Sox9 expression. This suggests a new hierarchical scheme whereby a Prrx1–Sox9 axis may influence the emergence of acinar–ductal metaplasia and regeneration. Furthermore, our data provide a possible explanation of why pancreatic cancer is skewed toward a ductal fate.
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PRRX1 promotes EMT in cancers.
“while PRRX1 also promotes EMT in cancers (58,59).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [58]
The Results section reports that Prrx1 isoforms increase migration and invasion in pancreatic cancer cells, and that Prrx1b overexpression disrupts cyst organization. These findings support related cancer-cell behaviours, but our copy does not show that PRRX1 promotes epithelial-to-mesenchymal transition (EMT), nor does it establish the claim across cancers generally. (LLM, conf=0.82)
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References 39 · Cited by 112
Research works printed but not linked: 1
- Gittes G. 2009. Developmental biology of the pancreas: A comprehensive review. Dev Biol 326: 4-35.
- Authors
- Reichert, M., Takano, S., von Burstin, J., Kim, S.-B., Lee, J.-S., Ihida-Stansbury, K., Hahn, C., Heeg, S., Schneider, G., Rhim, A. D., Stanger, B. Z., & Rustgi, A. K.
- Affiliations
- University of Pennsylvania (US)
- The University of Texas MD Anderson Cancer Center (US)
- Technical University of Munich (DE)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-01-25
- Volume
- 27
- Issue
- 3
- Pages
- 288-300
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3576514
- OpenAlex
- W2145672497
- Cited by
- 112
- References
- 39
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 9 · 2018: 5 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 9 · 2013: 8
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- University of Pennsylvania
- Honjo International Scholarship Foundation
- Deutsche Krebshilfe
- National Institutes of Health (DK050306)
- National Cancer Institute (CA117969, P01CA117969, P30CA016520)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-050306, DP2DK083111, K08DK088945, T32DK007066, DK007066, DK060694, DK088945, DK083111, R01DK083355, DK083355, R01DK060694, P30DK050306)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- PRRX1, homeodomain transcription factor, pancreatic regeneration, pancreatic carcinogenesis, acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia, pancreatic ductal adenocarcinoma, SOX9, chronic pancreatitis, cell migration and invasion, pancreatic ductal cells
- MeSH terms
- Animals, Cells, Cultured, Gene Expression Regulation, Mice, Inbred C57BL, Pancreas, Pancreatic Neoplasms, Promoter Regions, Genetic, Protein Binding, Regeneration, Homeodomain Proteins, Protein Isoforms, Gene Expression Profiling, Cell Line, Tumor, Mice, SOX9 Transcription Factor
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