ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
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- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Review
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Remote ischemia precondition protects against renal IRI through apoptosis associated vesicles carrying MIF protein via modulating DUSP6/JNK signaling axis.Journal of nanobiotechnology · 2025Article
- Aloin protects against UVB-induced apoptosis by modulating integrated signaling pathways.Frontiers in pharmacology · 2025Article
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- IKZF1 and BTG1 silencing reduces glucocorticoid response in B-cell precursor acute leukemia cell line.Hematology, transfusion and cell therapy · 2024Article
- DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.EMBO molecular medicine · 2024Article
- Overexpression of CENPU promotes cancer growth and metastasis and is associated with poor survival in patients with nasopharyngeal carcinoma.Translational cancer research · 2024Article
- Revealing the Complete Bispecific Phosphatase Genes (DUSPs) across the Genome and Investigating the Expression Patterns of GH_A11G3500 Resistance againstInternational journal of molecular sciences · 2024Article
- MicroRNAs in the Pathogenesis of Preeclampsia-A Case-Control In Silico Analysis.Current issues in molecular biology · 2024Article
- DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.Purinergic signalling · 2024Article
- Diltiazem Hydrochloride Protects Against Myocardial Ischemia/Reperfusion Injury in a BNIP3L/NIX-Mediated Mitophagy Manner.Journal of inflammation research · 2024Article
- LncTUG1 ameliorates renal tubular fibrosis in experimental diabetic nephropathy through the miR-145-5p/dual-specificity phosphatase 6 axis.Renal failure · 2023Article
- DUSP1 protects against ischemic acute kidney injury through stabilizing mtDNA via interaction with JNK.Cell death & disease · 2023Article
- Role of single-cell ferroptosis regulation in intercellular communication and skin cutaneous melanoma progression and immunotherapy.Cancer immunology, immunotherapy : CII · 2023Article
- Epstein-Barr virus-encoded miR-BART11-3p modulates the DUSP6-MAPK axis to promote gastric cancer cell proliferation and metastasis.Journal of virology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
purposeIn neurofibromatosis type 1 (NF1) and in highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), constitutively active RAS-GTP and increased MAPK signaling are important in tumorigenesis. Dual specificity phosphatases (DUSPs) are negative regulators of MAPK signaling that dephosphorylate p38, JNK, and ERK in different settings. Although often acting as tumor suppressors, DUSPs may also act as oncogenes, helping tumor cells adapt to high levels of MAPK signaling. We hypothesized that inhibiting DUSPs might be selectively toxic to cells from NF1-driven tumors. EXPERIMENTAL
designWe examined DUSP gene and protein expression in neurofibroma and MPNSTs. We used small hairpin RNA (shRNA) to knock down DUSP1 and DUSP6 to evaluate cell growth, downstream MAPK signaling, and mechanisms of action. We evaluated the DUSP inhibitor, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), in MPNST cell lines and in cell-line and patient-derived MPNST xenografts.
resultsDUSP1 and DUSP6 are expressed in NF1-deleted tumors. Knockdown of DUSP1 and DUSP6, alone or in combination, reduced MPNST cell growth and led to ERK and JNK hyperactivation increasing downstream TP53 and p-ATM. The DUSP inhibitor, BCI, diminished the survival of NF1-deleted Schwann cells and MPNST cell lines through activation of JNK.
conclusionsTargeting DUSP1 and DUSP6 genetically or with BCI effectively inhibits MPNST cell growth and promotes cell death,
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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.