ArticleThe Journal of clinical investigation2023
HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 44 citations in OpenAlex.
- HMGA1 and HMGA2: epigenetic regulators in myeloproliferative neoplasms and novel platelet transcriptomic biomarkers of myelofibrosis.Leukemia · 2026Article
- Pan-cancer characterization ofTranslational cancer research · 2026Article
- Dual Targeting of FGFR4 and PI3K-mTOR Suppresses Tumor-Associated Phenotypes in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2026Article
- Causal immune-inflammation mapping of the GERD-Barrett-adenocarcinoma cascade identifies FGF19-HLA-DR⁺ T-cell axis driving esophagogastric junction metaplasia.Journal of translational medicine · 2026Article
- Association of Arylacetamide Deacetylase-Mediated Extracellular Matrix Remodeling With Immune Exclusion in Pancreatic Cancer.World journal of oncology · 2026Article
- Identification of Key Genes Regulated by Lactylation Modification and Associated with Tumor Immune Microenvironment in Breast Cancer.Current issues in molecular biology · 2026Article
- Review
- Defining the cellular and molecular identities of histologic subtypes in lung adenocarcinoma.Experimental hematology & oncology · 2026Article
- Psammaplysene D overcomes sorafenib resistance in liver cancer by targeting FGFR4/CYP26A1-retinoic acid axis to drive ferroptosis.Journal of experimental & clinical cancer research : CR · 2026Article
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- Exploring prognostic genes related to lactylation and programmed cell death in pancreatic ductal adenocarcinoma: a comprehensive study combining bulk transcriptomics and experimental verification.Frontiers in genetics · 2026Article
- HMGA1 Activates FGFBP1 Transcription to Enhance Angiogenesis Induction and Tumor Progression via FGF2/FGFR1 Pathway.International journal of biological sciences · 2026Article
- Chemotherapy enhances HMGA1 secretion through the mutant p53-CK2 axis in pancreatic ductal adenocarcinoma cells.Cell death & disease · 2025Article
- FAIM modulates HCC progression via enhancing HMGA1 interaction with CDK7 and promoting its phosphorylation level.Journal of translational medicine · 2025Article
- Prognostic Significance of HMGA1 in Hepatocellular Carcinoma: Implications for Tumor Progression and Targeted Therapy.Archives of Iranian medicine · 2025Article
- HMGA1 promotes the progression of lung adenocarcinoma through the STAT1-mediated transcriptional activation of DDAH1.Biology direct · 2025Article
- Impact of HMGA1 on tumorigenesis, prognosis and immune microenvironment in HNSCC: a multi-omics study.NPJ precision oncology · 2025Article
- High mobility group A1 (HMGA1) promotes esophageal squamous cell carcinoma progression by inhibiting STING-mediated anti-tumor immunity.Nature communications · 2025Article
- Review
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High mobility group A1 (HMGA1) chromatin regulators are upregulated in diverse tumors where they portend adverse outcomes, although how they function in cancer remains unclear. Pancreatic ductal adenocarcinomas (PDACs) are highly lethal tumors characterized by dense desmoplastic stroma composed predominantly of cancer-associated fibroblasts and fibrotic tissue. Here, we uncover an epigenetic program whereby HMGA1 upregulates FGF19 during tumor progression and stroma formation. HMGA1 deficiency disrupts oncogenic properties in vitro while impairing tumor inception and progression in KPC mice and subcutaneous or orthotopic models of PDAC. RNA sequencing revealed HMGA1 transcriptional networks governing proliferation and tumor-stroma interactions, including the FGF19 gene. HMGA1 directly induces FGF19 expression and increases its protein secretion by recruiting active histone marks (H3K4me3, H3K27Ac). Surprisingly, disrupting FGF19 via gene silencing or the FGFR4 inhibitor BLU9931 recapitulates most phenotypes observed with HMGA1 deficiency, decreasing tumor growth and formation of a desmoplastic stroma in mouse models of PDAC. In human PDAC, overexpression of HMGA1 and FGF19 defines a subset of tumors with extremely poor outcomes. Our results reveal what we believe is a new paradigm whereby HMGA1 and FGF19 drive tumor progression and stroma formation, thus illuminating FGF19 as a rational therapeutic target for a molecularly defined PDAC subtype.
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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.