ArticlePloS one2017
DUSP5 and DUSP6, two ERK specific phosphatases, are markers of a higher MAPK signaling activation in BRAF mutated thyroid cancers.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma.Journal of cellular and molecular medicine · 2023Pooled it
- Rivaroxaban suppresses factor Xa-Driven PAR-2-ERK inflammatory, catabolic, osteoclastogenic, and mitochondrial dysfunction signaling in osteoarthritis-relevant chondrocytes: a drug-repurposing strategy for joint inflammation.Frontiers in pharmacology · 2026Article
- Co-trimoxazole-induced reproductive toxicity and placental-barrier disruption: impact on cell-cell junctions and ERK signaling pathway.Frontiers in cell and developmental biology · 2026Article
- Molecular Frameworks for ERK1/2 Inhibition: Lessons from Synthetic and SAR Explorations.ACS omega · 2025Review
- Mesalazine RegulatesPharmaceutics · 2025Article
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Deciphering the history of ERK activity from fixed-cell immunofluorescence measurements.Nature communications · 2025Article
- PSMC6 regulation of ovarian cancer cisplatin resistance unravels a new mode for proteasome targeting.International journal of biological sciences · 2025Article
- MAPK/ERK signaling pathway in rheumatoid arthritis: mechanisms and therapeutic potential.PeerJ · 2025Review
- Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.Briefings in bioinformatics · 2024Article
- eIF4F controls ERK MAPK signaling in melanomas withProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting DUSP5 suppresses malignant phenotypes of BRAF-mutant thyroid cancer cells and improves their response to sorafenib.Endocrine · 2024Article
- DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-β/Smad signaling pathway in lung adenocarcinoma.Cancer cell international · 2024Article
- Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.Cell death and differentiation · 2024Article
- Human surface ectoderm and amniotic ectoderm are sequentially specified according to cellular density.Science advances · 2024Article
- mPFC DUSP1 mediates adolescent cocaine exposure-induced higher sensitivity to drug in adulthood.EMBO reports · 2023Article
- In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments.Cancers · 2023Article
- Combination Therapy With MDM2 and MEK Inhibitors Is Effective in Patient-Derived Models of Lung Adenocarcinoma With Concurrent Oncogenic Drivers and MDM2 Amplification.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- The Role ofViruses · 2023Article
- The first-in-class ERK inhibitor ulixertinib shows promising activity in mitogen-activated protein kinase (MAPK)-driven pediatric low-grade glioma models.Neuro-oncology · 2023Article
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMolecular alterations of the MAPK pathway are frequently observed in papillary thyroid carcinomas (PTCs). It leads to a constitutive activation of the signalling pathway through an increase in MEK and ERK phosphorylation. ERK is negatively feedback-regulated by Dual Specificity Phosphatases (DUSPs), especially two ERK-specific DUSPs, DUSP5 (nuclear) and DUSP6 (cytosolic). These negative MAPK regulators may play a role in thyroid carcinogenesis.
methodsMAPK pathway activation was analyzed in 11 human thyroid cancer cell lines. Both phosphatases were studied in three PCCL3 rat thyroid cell lines that express doxycycline inducible PTC oncogenes (RET/PTC3, H-RASV12 or BRAFV600E). Expression levels of DUSP5 and DUSP6 were quantified in 39 human PTCs. The functional role of DUSP5 and DUSP6 was investigated through their silencing in two human BRAFV600E carcinoma cell lines.
resultsBRAFV600E human thyroid cancer cell lines expressed higher phospho-MEK levels but not higher phospho-ERK levels. DUSP5 and DUSP6 are specifically induced by the MEK-ERK pathway in the three PTC oncogenes inducible thyroid cell lines. This negative feedback loop explains the tight regulation of p-ERK levels. DUSP5 and DUSP6 mRNA are overexpressed in human PTCs, especially in BRAFV600E mutated PTCs. DUSP5 and/or DUSP6 siRNA inactivation did not affect proliferation in two BRAFV600E mutated cell lines, which may be explained by a compensatory increase in other phosphatases. In the light of this, we observed a marked DUSP6 upregulation upon DUSP5 inactivation. Despite this, DUSP5 and DUSP6 positively control cell migration and invasion.
conclusionsOur results are in favor of a stronger activation of the MAPK pathway in BRAFV600E PTCs. DUSP5 and DUSP6 have pro-tumorigenic properties in two BRAFV600E PTC cell line models.
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