ArticleThe Journal of experimental medicine2015
DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 69 citations in OpenAlex.
- METTL3 stabilizes FASN mRNA by mediating mCell & bioscience · 2026Article
- The novel role of DUSP4 in suppressing ferroptosis and promoting cytotoxicity of CD8British journal of cancer · 2025Article
- Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells.Nature communications · 2025Article
- Genetic and Epigenetic Aberrations ofCurrent issues in molecular biology · 2025Article
- Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.Acta pharmacologica Sinica · 2024Article
- Cellular and clinical impact of protein phosphatase enzyme epigenetic silencing in multiple cancer tissues.Human genomics · 2024Article
- DUSP4 inhibits autophagic cell death and apoptosis in colorectal cancer by regulating BCL2-Beclin1/Bax signaling.Molecular biology reports · 2023Article
- Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.International journal of molecular sciences · 2022Review
- Combination of BMI1 and MAPK/ERK inhibitors is effective in medulloblastoma.Neuro-oncology · 2022Article
- Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer.Breast cancer research : BCR · 2022Article
- GFAPδ: A Promising Biomarker and Therapeutic Target in Glioblastoma.Frontiers in oncology · 2022Review
- Loss of DUSP4 Expression as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.Diagnostics (Basel, Switzerland) · 2021Article
- Aberrant expression of DUSP4 is a specific phenomenon in betel quid-related oral cancer.Medical molecular morphology · 2021Article
- Selective inhibitors for JNK signalling: a potential targeted therapy in cancer.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Requirement for LIM kinases in acute myeloid leukemia.Leukemia · 2020Article
- Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers.Genes, chromosomes & cancer · 2020Article
- Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β-mediated colitis.The Journal of clinical investigation · 2020Article
- Dysregulation of Dual-Specificity Phosphatases by Epstein-Barr Virus LMP1 and Its Impact on Lymphoblastoid Cell Line Survival.Journal of virology · 2020Article
- Phosphorylation Dynamics of JNK Signaling: Effects of Dual-Specificity Phosphatases (DUSPs) on the JNK Pathway.International journal of molecular sciences · 2019Review
- Pharmacological DNA demethylation restores SMAD1 expression and tumor suppressive signaling in diffuse large B-cell lymphoma.Blood advances · 2019Article
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7 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The epigenetic dysregulation of tumor suppressor genes is an important driver of human carcinogenesis. We have combined genome-wide DNA methylation analyses and gene expression profiling after pharmacological DNA demethylation with functional screening to identify novel tumor suppressors in diffuse large B cell lymphoma (DLBCL). We find that a CpG island in the promoter of the dual-specificity phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL, irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75% of >200 examined cases. The DUSP4 genomic locus is further deleted in up to 13% of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic factor in three independent cohorts of DLBCL patients. Ectopic expression of wild-type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo and synergizes strongly with the Bruton's tyrosine kinase inhibitor ibrutinib. Our results indicate that DLBCL cells depend on JNK signaling for survival. This finding provides a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of chronic active B cell receptor signaling.
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