ArticleCell reports2020
Hotspots of Aberrant Enhancer Activity in Fibrolamellar Carcinoma Reveal Candidate Oncogenic Pathways and Therapeutic Vulnerabilities.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Overcoming CXCR4-Mediated T-Cell Exclusion Potentiates Antitumor Cytotoxicity in Fibrolamellar Carcinoma.Gastroenterology · 2026Article
- Single-nucleus ATAC-seq analysis resolves chromatin and transcriptional features of fibrolamellar carcinoma.Scientific reports · 2026Article
- Article
- Coordinated gene expression within sustained STAT3-associated chromatin conformations contributes to hepatocellular carcinoma progression.Cancer communications (London, England) · 2025Article
- Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma.Science advances · 2025Article
- A novel high-throughput screening platform to identify inhibitors of DNAJB1-PRKACA-driven transcriptional activity in fibrolamellar carcinoma.SLAS discovery : advancing life sciences R & D · 2025Article
- DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.Cancer discovery · 2025Article
- Machine learning tools for deciphering the regulatory logic of enhancers in health and disease.Frontiers in genetics · 2025Review
- A Case of Fibrolamellar Hepatocellular Carcinoma in Which Tumor Control Was Achieved by Re-Administering Atezolizumab and Bevacizumab.Cancer reports (Hoboken, N.J.) · 2024Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Distinct phases of cellular signaling revealed by time-resolved protein synthesis.Nature chemical biology · 2024Article
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma.PLoS genetics · 2024Article
- Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.Cell reports · 2024Article
- Models of fibrolamellar carcinomas, tools for evaluation of a new era of treatments.Frontiers in immunology · 2024Review
- The Typical tRNA Co-Expresses Multiple 5' tRNA Halves Whose Sequences and Abundances Depend on Isodecoder and Isoacceptor and Change with Tissue Type, Cell Type, and Disease.Non-coding RNA · 2023Article
- Discovery and Synthesis of a Naturally Derived Protein Kinase Inhibitor that Selectively Inhibits Distinct Classes of Serine/Threonine Kinases.Journal of natural products · 2023Article
- Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss.Nature communications · 2023Article
- Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.eLife · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Fibrolamellar carcinoma (FLC) is a rare, therapeutically intractable liver cancer that disproportionately affects youth. Although FLC tumors exhibit a distinct gene expression profile, the chromatin regulatory landscape and the genes most critical for tumor cell survival remain unclear. Here, we use chromatin run-on sequencing to discover ∼7,000 enhancers and 141 enhancer hotspots activated in FLC relative to nonmalignant liver. Bioinformatic analyses reveal aberrant ERK/MEK signaling and candidate master transcriptional regulators. We also define the genes most strongly associated with hotspots of FLC enhancer activity, including CA12 and SLC16A14. Treatment of FLC cell models with inhibitors of CA12 or SLC16A14 independently reduce cell viability and/or significantly enhance the effect of the MEK inhibitor cobimetinib. These findings highlight molecular targets for drug development, as well as drug combination approaches.
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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.