ArticleCarcinogenesis2022
Dysregulation of HNF1B/Clusterin axis enhances disease progression in a highly aggressive subset of pancreatic cancer patients.
Article in Carcinogenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 52 citations in OpenAlex.
- A HRH1-YAP1 feedback loop drives pancreatic cancer progression and predicts therapeutic response.Oncology letters · 2026Article
- Relationship Between PTBP1 and Pancreatic Cancer Based on microRNA and Behavior During TYMS-Mediated Carcinogenesis.Cancer science · 2026Article
- A TRPM4-associated necrotic cell death signature for prognostic stratification in pancreatic cancer.Journal of gastrointestinal oncology · 2026Article
- A tumor microenvironment integrated (TMI) staging system for pancreatic ductal adenocarcinoma based on cancer-associated fibroblast and molecular consensus signatures.Discover oncology · 2026Article
- Characterization of a pancreatic cancer GWAS signal suggests PDX1 buffers stress in the exocrine pancreas.medRxiv : the preprint server for health sciences · 2026Article
- Computational theranostics strategy for pancreatic ductal adenocarcinoma.Molecular diversity · 2026Article
- DNA methylation-mediated silencing of HNF1B promotes bladder cancer progression.Clinical epigenetics · 2026Article
- Estrogen Production in Pancreatic Cancer Shapes a Tumor-Suppressive Stromal Microenvironment.Cancer research · 2026Article
- PRECOG update: an augmented resource of clinical outcome associations with gene expression for adult, pediatric, and immunotherapy cohorts.Nucleic acids research · 2026Article
- Systemic control of HNF1B-driven redox homeostasis by N6-adenosine methylation.Nucleic acids research · 2026Article
- Article
- Transcription factor-driven metabolic stratification reveals glycolytic and lipogenic subtypes with distinct prognostic and functional features in pancreatic cancer.Frontiers in oncology · 2026Article
- Transcriptomic Analyses of Normal Human Pancreata Reveal the Presence of Cancer Subtypes that Correlate with Acinar Ductal Metaplasia and Donor Ancestry.Cancer research communications · 2026Article
- Identification of key genes in pancreatic ductal adenocarcinoma with biologically informed deep neural network.Journal of gastrointestinal oncology · 2025Article
- The TET3/GATA6 Axis Drives Lipid Metabolism and Therapeutic Vulnerabilities in Pancreatic Ductal Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- OCIAD2 as a novel prognostic and therapeutic biomarker for pancreatic cancer: A study based on transcriptomic signature and bioinformatics analysis.PLoS computational biology · 2025Article
- CX26 promotes pancreatic cancer progression by competitively inhibiting interaction of c-Myc with PSMD2 and enhancing c-Myc stability.Journal of translational medicine · 2025Article
- Efficacy of NAMPT Inhibitors in Pancreatic Cancer After Stratification by MAP17 (PDZK1IP1) Levels.Cancers · 2025Article
- Identification of Anticancer Target Combinations to Treat Pancreatic Cancer and Its Associated Cachexia Using Constraint-Based Modeling.Molecules (Basel, Switzerland) · 2025Article
- Single-cell transcriptional dissection illuminates an evolution of immunosuppressive microenvironment during pancreatic ductal adenocarcinoma metastasis.Signal transduction and targeted therapy · 2025Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy and is largely refractory to available treatments. Identifying key pathways associated with disease aggressiveness and therapeutic resistance may characterize candidate targets to improve patient outcomes. We used a strategy of examining the tumors from a subset of PDAC patient cohorts with the worst survival to understand the underlying mechanisms of aggressive disease progression and to identify candidate molecular targets with potential therapeutic significance. Non-negative matrix factorization (NMF) clustering, using gene expression profile, revealed three patient subsets. A 142-gene signature specific to the subset with the worst patient survival, predicted prognosis and stratified patients with significantly different survival in the test and validation cohorts. Gene-network and pathway analysis of the 142-gene signature revealed dysregulation of Clusterin (CLU) in the most aggressive patient subset in our patient cohort. Hepatocyte nuclear factor 1 b (HNF1B) positively regulated CLU, and a lower expression of HNF1B and CLU was associated with poor patient survival. Mechanistic and functional analyses revealed that CLU inhibits proliferation, 3D spheroid growth, invasiveness and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cell lines. Mechanistically, CLU enhanced proteasomal degradation of EMT-regulator, ZEB1. In addition, orthotopic transplant of CLU-expressing pancreatic cancer cells reduced tumor growth in mice. Furthermore, CLU enhanced sensitivity of pancreatic cancer cells representing aggressive patient subset, to the chemotherapeutic drug gemcitabine. Taken together, HNF1B/CLU axis negatively regulates pancreatic cancer progression and may potentially be useful in designing novel strategies to attenuate disease progression in PDAC patients.
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