ArticleOncogene2014
MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 100 citations in OpenAlex.
- Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial.JAMA oncology · 2017Trial
- Acyclic Retinoid Attenuates STAT3 Signaling and Reduces In Vitro Growth of A375-Derived Dabrafenib Plus Trametinib-Resistant Melanoma Cells.International journal of molecular sciences · 2026Article
- Integrated approaches to sensitizing melanoma to radiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Review
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Article
- Advancements on the synergistic application of oncolytic viruses and molecularly targeted therapies for the treatment of solid tumors (Review).International journal of oncology · 2026Review
- Phenotype switching in highly invasive resistant to vemurafenib and cobimetinib melanoma cells.Cell communication and signaling : CCS · 2025Article
- High-throughput drug screening in advanced pre-clinical 3D melanoma models identifies potential first-line therapies for NRAS-mutated melanoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Sensitivity to immune checkpoint inhibitors in BRAF/MEK inhibitor refractory melanoma.Journal for immunotherapy of cancer · 2025Article
- A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).BMC cancer · 2025Article
- CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.Haematologica · 2024Article
- Exploring resistance to immune checkpoint inhibitors and targeted therapies in melanoma.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- A distinct pattern of growth and RAC1 signaling in melanoma brain metastasis cells.Neuro-oncology · 2023Article
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- From simplicity to complexity in current melanoma models.Experimental dermatology · 2022Review
- Melanocyte stem cells in skin diseases and their potential in cell-based therapy.Histology and histopathology · 2022Review
- Inhibition of MEK-ERK pathway enhances oncolytic vaccinia virus replication in doxorubicin-resistant ovarian cancer.Molecular therapy oncolytics · 2022Article
- Review
- Salviolone fromInternational journal of molecular sciences · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated activity of the mitogen-activated protein kinase (MAPK) signaling cascade is found in the majority of human melanomas and is known to regulate proliferation, survival and invasion. Current targeted therapies focus on decreasing the activity of this pathway; however, we do not fully understand how these therapies impact tumor biology, especially given that melanoma is a heterogeneous disease. Using a three-dimensional (3D), collagen-embedded spheroid melanoma model, we observed that MEK and BRAF inhibitors can increase the invasive potential of ∼20% of human melanoma cell lines. The invasive cell lines displayed increased receptor tyrosine kinase (RTK) activity and activation of the Src/FAK/signal transducers and activators of transcription-3 (STAT3) signaling axis, also associated with increased cell-to-cell adhesion and cadherin engagement following MEK inhibition. Targeting various RTKs, Src, FAK and STAT3 with small molecule inhibitors in combination with a MEK inhibitor prevented the invasive phenotype, but only STAT3 inhibition caused cell death in the 3D context. We further show that STAT3 signaling is induced in BRAF-inhibitor-resistant cells. Our findings suggest that MEK and BRAF inhibitors can induce STAT3 signaling, causing potential adverse effects such as increased invasion. We also provide the rationale for the combined targeting of the MAPK pathway along with inhibitors of RTKs, SRC or STAT3 to counteract STAT3-mediated resistance phenotypes.
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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.