ArticleScience signaling2014
BRAF inhibitors induce metastasis in RAS mutant or inhibitor-resistant melanoma cells by reactivating MEK and ERK signaling.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- The end of the genetic paradigm of cancer.PLoS biology · 2025Review
- Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.Scientific reports · 2025Article
- Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.Cell reports · 2024Article
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- SOX10 deficiency-mediated LAMB3 upregulation determines the invasiveness of MAPKi-resistant melanoma.Oncogene · 2024Article
- Article
- Exploring the In Vitro and In Vivo Therapeutic Potential of BRAF and MEK Inhibitor Combination in NRAS-Mutated Melanoma.Cancers · 2023Article
- A Therapeutic Vaccine in Combination with Cyclic GMP-AMP Cures More Differentiated Melanomas in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Novel strategy for oncogenic alteration-induced lipid metabolism reprogramming in pancreatic cancer.Acta biochimica et biophysica Sinica · 2023Review
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma.Cell communication and signaling : CCS · 2022Article
- Diabetes and skin cancers: Risk factors, molecular mechanisms and impact on prognosis.World journal of clinical cases · 2022Review
- Vemurafenib Drives Epithelial-to-Mesenchymal Transition Gene Expression in BRAF Inhibitor‒Resistant BRAFThe Journal of investigative dermatology · 2022Article
- Functionalized Lineage Tracing Can Enable the Development of Homogenization-Based Therapeutic Strategies in Cancer.Frontiers in immunology · 2022Article
- Aquaporins in Cancer Biology.Frontiers in oncology · 2022Review
- Targeting KRAS in pancreatic cancer: new drugs on the horizon.Cancer metastasis reviews · 2021Review
- Clinical cancer genomic profiling.Nature reviews. Genetics · 2021Review
- Emerging nanomedicine-based therapeutics for hematogenous metastatic cascade inhibition: Interfering with the crosstalk between "seed and soil".Acta pharmaceutica Sinica. B · 2021Review
- Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Melanoma is a highly metastatic and lethal form of skin cancer. The protein kinase BRAF is mutated in about 40% of melanomas, and BRAF inhibitors improve progression-free and overall survival in these patients. However, after a relatively short period of disease control, most patients develop resistance because of reactivation of the RAF-ERK (extracellular signal-regulated kinase) pathway, mediated in many cases by mutations in RAS. We found that BRAF inhibition induces invasion and metastasis in RAS mutant melanoma cells through a mechanism mediated by the reactivation of the MEK (mitogen-activated protein kinase kinase)-ERK pathway, increased expression and secretion of interleukin 8, and induction of protease-dependent invasion. These events were accompanied by a cell morphology switch from predominantly rounded to predominantly elongated cells. We also observed similar responses in BRAF inhibitor-resistant melanoma cells. These data show that BRAF inhibitors can induce melanoma cell invasion and metastasis in tumors that develop resistance to these drugs.
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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.