ArticleProceedings of the National Academy of Sciences of the United States of America2018
DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Research advances and treatment perspectives of pancreatic adenosquamous carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2023Pooled it
- Basal Marker ΔNp63α Is Enriched in Pancreatic Cancer Metastases but Not in Primary Tumors Post-Chemotherapy.Cancer medicine · 2026Article
- Twist1 overexpression models an aggressive subtype of pancreatic ductal adenocarcinoma in vivo.Lab animal · 2026Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Nature communications · 2026Article
- The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026Review
- [Research progress in clinical pathology and molecular mechanisms of pancreatic adenosquamous carcinoma].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Review
- Epigenetic context defines the transcriptional activity of canonical and noncanonical NF-κB signaling in pancreatic cancer.Cell death discovery · 2026Article
- Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.Gastroenterology report · 2026Review
- Transcriptional pause release at enhancers mediates cell identity.NAR cancer · 2025Review
- KLF5 enables dichotomous lineage programs in pancreatic cancer via the AAA+ ATPase coactivators RUVBL1 and RUVBL2.Nature communications · 2025Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Research square · 2025Article
- Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.Nature communications · 2025Article
- Comprehensive multi-omics profiling identifies novel molecular subtypes of pancreatic ductal adenocarcinoma.Genes & diseases · 2024Review
- Interaction between MED12 and ΔNp63 activates basal identity in pancreatic ductal adenocarcinoma.Nature genetics · 2024Article
- Critical Differential Expression Assessment for Individual Bulk RNA-Seq Projects.bioRxiv : the preprint server for biology · 2024Article
- Epigenetic control of pancreatic cancer metastasis.Cancer metastasis reviews · 2023Review
- ΔNp63α-mediated epigenetic regulation in keratinocyte senescence.Epigenetics · 2023Article
- Marker-based CRISPR screening reveals a MED12-p63 interaction that activates basal identity in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2023Article
- High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival.NPJ precision oncology · 2023Article
- BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer.Scientific reports · 2023Article
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2 authors.
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Abstract
Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival. Importantly, depletion of deltaNp63 in these systems significantly decreased cell proliferation and gene expression patterns associated with a squamous subtype and transcriptionally mimicked a subtype switch. Using genomic localization data of deltaNp63 in pancreatic cancer cell lines coupled with epigenome mapping data from patient-derived xenografts, we uncovered that deltaNp63 mainly exerts its effects by activating subtype-specific super enhancers. Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63. Genes associated with these enhancers included a network of transcription factors, including HIF1A, BHLHE40, and RXRA, which form a highly intertwined transcriptional regulatory network with deltaNp63 to further activate downstream genes associated with poor survival.
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