ArticleOncogene2018
ERK5 is activated by oncogenic BRAF and promotes melanoma growth.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- A different MAPK, ERK5 plays a critical role in cell specification and differentiation.Biochemistry and biophysics reports · 2026Review
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Refined Phylogenetic Ortholog Inference Reveals Coevolutionary Expansion of the MAPK Signaling Network Through Finetuning of Pathway Specificity.Journal of molecular evolution · 2025Article
- The MEK5/ERK5 pathway promotes the activation of the Hedgehog/GLI signaling in melanoma cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy.Signal transduction and targeted therapy · 2025Article
- Linc00239 Promotes Colorectal Cancer Development via MicroRNA-182-5p/Metadherin Axis.Biochemical genetics · 2024Article
- Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells.Cell communication and signaling : CCS · 2024Article
- Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications.Experimental & molecular medicine · 2023Article
- Review
- Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy.Journal of medicinal chemistry · 2023Review
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- Kisspeptins and norepinephrine regulate different G-protein-coupled receptor signaling pathways.Translational lung cancer research · 2022Article
- Inhibition of ERK5 Elicits Cellular Senescence in Melanoma via the Cyclin-Dependent Kinase Inhibitor p21.Cancer research · 2022Article
- Review
- MAPK inhibitors dynamically affect melanoma release of immune NKG2D-ligands, as soluble protein and extracellular vesicle-associated.Frontiers in cell and developmental biology · 2022Article
- ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled?Frontiers in cell and developmental biology · 2022Review
- ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology.Journal of cellular and molecular medicine · 2021Article
- ERK5 modulates IL-6 secretion and contributes to tumor-induced immune suppression.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant melanoma is among the most aggressive cancers and its incidence is increasing worldwide. Targeted therapies and immunotherapy have improved the survival of patients with metastatic melanoma in the last few years; however, available treatments are still unsatisfactory. While the role of the BRAF-MEK1/2-ERK1/2 pathway in melanoma is well established, the involvement of mitogen-activated protein kinases MEK5-ERK5 remains poorly explored. Here we investigated the function of ERK5 signaling in melanoma. We show that ERK5 is consistently expressed in human melanoma tissues and is active in melanoma cells. Genetic silencing and pharmacological inhibition of ERK5 pathway drastically reduce the growth of melanoma cells and xenografts harboring wild-type (wt) or mutated BRAF (V600E). We also found that oncogenic BRAF positively regulates expression, phosphorylation, and nuclear localization of ERK5. Importantly, ERK5 kinase and transcriptional transactivator activities are enhanced by BRAF. Nevertheless, combined pharmacological inhibition of BRAFV600E and MEK5 is required to decrease nuclear ERK5, that is critical for the regulation of cell proliferation. Accordingly, combination of MEK5 or ERK5 inhibitors with BRAFV600E inhibitor vemurafenib is more effective than single treatments in reducing colony formation and growth of BRAFV600E melanoma cells and xenografts. Overall, these data support a key role of the ERK5 pathway for melanoma growth in vitro and in vivo and suggest that targeting ERK5, alone or in combination with BRAF-MEK1/2 inhibitors, might represent a novel approach for melanoma treatment.
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Registered trials
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.