ArticleThe Journal of clinical investigation2015
STK4 regulates TLR pathways and protects against chronic inflammation-related hepatocellular carcinoma.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Autoantibodies in cancer: a systematic review of their clinical role in the most prevalent cancers.Frontiers in immunology · 2024Pooled it
- The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.Cell · 2021Trial
- MST1 bridges LYN and SHP-1 to suppress FcεRI-mediated mast cell activation and allergic responses.Cellular & molecular immunology · 2026Article
- Molecular regulation by ubiquitin-specific proteases (USPs) in HCC: cell cycle, oncogenic signaling, and beyond.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Hippo terminal effector YAP boosts enterovirus replication in type 1 diabetes.Nature communications · 2025Article
- Integrative analysis of exosomal ncRNAs and their regulatory networks in liver cancer progression.Practical laboratory medicine · 2025Article
- The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases.MedComm · 2025Review
- Photon-triggered pyroptosis and ferroptosis dual-functional nanoplatform for cancer immunotherapy.Light, science & applications · 2025Article
- A self-assembling nanoplatform for pyroptosis and ferroptosis enhanced cancer photoimmunotherapy.Light, science & applications · 2025Article
- Screening of Candidate Inflammatory Markers of Epithelial Cells in Hepatocellular Carcinoma based on Integration Analysis of TCGA/ICGC Databases and Single-cell Sequencing.Recent patents on anti-cancer drug discovery · 2025Article
- Hepatocellular carcinoma: pathogenesis, molecular mechanisms, and treatment advances.Frontiers in oncology · 2025Review
- Macrophage MST1 protects against schistosomiasis-induced liver fibrosis by promoting the PPARγ-CD36 pathway and suppressing NF-κB signaling.PLoS pathogens · 2024Article
- YAP mediates HIV-related liver fibrosis.JHEP reports : innovation in hepatology · 2024Article
- Identification and validation of a novel innate lymphoid cell-based signature to predict prognosis and immune response in liver cancer by integrated single-cell RNA analysis and bulk RNA sequencing.Translational cancer research · 2024Article
- Genome-Wide Methylation Profiling of Peripheral T-Cell Lymphomas Identifies TRIP13 as a Critical Driver of Tumor Proliferation and Survival.Epigenomes · 2024Article
- Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease.Science China. Life sciences · 2024Article
- A novel anoikis-related gene signature can predict the prognosis of hepatocarcinoma patients.Translational cancer research · 2024Article
- Genome-wide methylation profiling of Peripheral T-cell lymphomas identifies TRIP13 as a critical driver of tumor proliferation and survival.Research square · 2024Article
- Inactivation of MST1/2 Controls Macrophage Polarization to Affect Macrophage-Related Disease via YAP and Non-YAP Mechanisms.International journal of biological sciences · 2024Article
- The role of non-canonical Hippo pathway in regulating immune homeostasis.European journal of medical research · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is frequently associated with pathogen infection-induced chronic inflammation. Large numbers of innate immune cells are present in HCCs and can influence disease outcome. Here, we demonstrated that the tumor suppressor serine/threonine-protein kinase 4 (STK4) differentially regulates TLR3/4/9-mediated inflammatory responses in macrophages and thereby is protective against chronic inflammation-associated HCC. STK4 dampened TLR4/9-induced proinflammatory cytokine secretion but enhanced TLR3/4-triggered IFN-β production via binding to and phosphorylating IL-1 receptor-associated kinase 1 (IRAK1), leading to IRAK1 degradation. Notably, macrophage-specific Stk4 deletion resulted in chronic inflammation, liver fibrosis, and HCC in mice treated with a combination of diethylnitrosamine (DEN) and CCl4, along with either LPS or E. coli infection. STK4 expression was markedly reduced in macrophages isolated from human HCC patients and was inversely associated with the levels of IRAK1, IL-6, and phospho-p65 or phospho-STAT3. Moreover, serum STK4 levels were specifically decreased in HCC patients with high levels of IL-6. In STK4-deficient mice, treatment with an IRAK1/4 inhibitor after DEN administration reduced serum IL-6 levels and liver tumor numbers to levels similar to those observed in the control mice. Together, our results suggest that STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC.
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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.