ArticleOncogene2021
Hepatic stellate cells promote intrahepatic cholangiocarcinoma progression via NR4A2/osteopontin/Wnt signaling axis.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting the CCL5/CCR5-PI3K-AKT axis suppresses hepatic stellate cell-induced breast cancer metastasis.Cancer cell international · 2026Article
- NR4A2 induces perineural invasion in head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma via CXCL5/CXCR2 signaling axis.Cancer letters · 2026Article
- Forsythiaside A inhibits the progression of intrahepatic cholangiocarcinoma partially via suppressing oxidative stress-induced hepatic stellate cell activation and macrophage polarization.BMC biotechnology · 2026Article
- Cross-Talk Between Tumor Cells and Stellate Cells Promotes Oncolytic VSV Activity in Intrahepatic Cholangiocarcinoma.Cancers · 2025Article
- Study of the effect of zinc oxide, selenium, and silver nanoparticles on the expression level of oxidative stress-associated genes in ovarian cancer.Medical oncology (Northwood, London, England) · 2025Article
- Osteopontin: an indispensable component in common liver, pancreatic, and biliary related disease.Journal of cancer research and clinical oncology · 2024Review
- CircMALAT1 promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma via the miR-512-5p/VCAM1 axis.Acta biochimica et biophysica Sinica · 2024Article
- Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma.Cell death discovery · 2024Article
- A novel eight-gene Immune Cell-Associated Predictive Gene model to predict recurrence in triple-negative breast cancer.Translational cancer research · 2023Article
- Targeting Microglial Metabolic Rewiring Synergizes with Immune-Checkpoint Blockade Therapy for Glioblastoma.Cancer discovery · 2023Article
- Secretome of senescent hepatic stellate cells favors malignant transformation from nonalcoholic steatohepatitis-fibrotic progression to hepatocellular carcinoma.Theranostics · 2023Article
- Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition.Journal of experimental & clinical cancer research : CR · 2022Article
- Chemical, Molecular, and Single-nucleus Analysis Reveal Chondroitin Sulfate Proteoglycan Aberrancy in Fibrolamellar Carcinoma.Cancer research communications · 2022Article
- Nurr1 Is Not an Essential Regulator of BDNF in Mouse Cortical Neurons.International journal of molecular sciences · 2022Article
- Expression profiling suggests the involvement of hormone-related, metabolic, and Wnt signaling pathways in pterygium progression.Frontiers in endocrinology · 2022Article
- NOV/CCN3 Promotes Cell Migration and Invasion in Intrahepatic Cholangiocarcinoma via miR-92a-3p.Genes · 2021Article
- TMEM88 Modulates Lipid Synthesis and Metabolism Cytokine by Regulating Wnt/β-Catenin Signaling Pathway in Non-Alcoholic Fatty Liver Disease.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a highly fatal malignancy characterized by a vast amount of intra-tumoral fibroblasts. These fibroblasts are potentially implicated in maintaining the high aggressiveness of ICC, whereas its pro-cancer mechanisms remain scarcely reported. Here, by establishing co-culture models of ICC cells and hepatic stellate cells (HSCs), we identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells. Functionally, NR4A2 promotes tumor proliferation, metastatic potentiality and represents an independent prognostic indicator for overall survival in ICC patients. Mechanistically, NR4A2 upregulates osteopontin (OPN) expression through transcriptional activation and thereby augments the activity of Wnt/β-catenin signaling. Intriguingly, in the context of co-culture, vascular endothelial growth factor (VEGF), a previously proved NR4A2 stimulus, not only enhances NR4A2 expression, but also can be blunted by the interference of the NR4A2-OPN axis. Altogether, this study suggests the NR4A2/OPN/Wnt signaling axis to be a pivotal executor of HSC-instigated cancer-promoting roles in ICC, and the NR4A2/OPN/VEGF positive feedback loop may help to reinforce the effect.
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