ArticleEMBO molecular medicine2022
Blockade of the pro-fibrotic reaction mediated by the miR-143/-145 cluster enhances the responses to targeted therapy in melanoma.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Extracellular matrix stiffness determines the phenotypic behavior of dedifferentiated melanoma cells through a DDR1/2-dependent YAP mechanotransduction pathway.Oncogenesis · 2026Article
- Uncovering the Intricate and Heterogeneous Cellular Microenvironment of Cutaneous Melanoma.Medicina (Kaunas, Lithuania) · 2026Review
- Therapy-induced mRNA, rRNA and tRNA methylation alterations confer tolerance phenotype in tumor cells: mechanism and implications.International journal of biological sciences · 2026Review
- Multiple roles of MicroRNAs in melanoma: biomarkers for diagnosis, prognosis, and treatment prediction.Frontiers in immunology · 2026Review
- CUL4B promotes hepatocellular carcinoma progression and oxaliplatin resistance by facilitating FUS degradation.Cell death & disease · 2025Article
- Comparison of in vitro migration assays evaluating nintedanib's migration inhibitory effects on melanoma cells.Scientific reports · 2025Article
- Phenotype switching in highly invasive resistant to vemurafenib and cobimetinib melanoma cells.Cell communication and signaling : CCS · 2025Article
- Article
- miR-145-5p Inhibits HER2-Positive Breast Cancer Cells via Targeting ARF6.International journal of general medicine · 2025Article
- TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.Cell death & disease · 2024Article
- Targeting MetaLnc9/miR-143/FSCN1 axis inhibits oxidative stress and myofibroblast transdifferentiation in oral submucous fibrosis.Journal of dental sciences · 2024Article
- Review
- Impact of Nintedanib and Anti-Angiogenic Agents on Uveal Melanoma Cell Behavior.Investigative ophthalmology & visual science · 2024Article
- Satellite cell-derived exosome-mediated delivery of microRNA-23a/27a/26a cluster ameliorates the renal tubulointerstitial fibrosis in mouse diabetic nephropathy.Acta pharmacologica Sinica · 2023Article
- Targeting FSCN1 with an oral small-molecule inhibitor for treating ocular neovascularization.Journal of translational medicine · 2023Article
- The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance.Oncogenesis · 2023Review
- Serum microRNAs in Systemic Sclerosis, Associations with Digital Vasculopathy and Lung Involvement.International journal of molecular sciences · 2022Article
- Review
- Antifibrotic drugs as therapeutic tools in resistant melanoma.EMBO molecular medicine · 2022Article
- Blockade of the pro-fibrotic reaction mediated by the miR-143/-145 cluster enhances the responses to targeted therapy in melanoma.EMBO molecular medicine · 2022Article
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lineage dedifferentiation toward a mesenchymal-like state displaying myofibroblast and fibrotic features is a common mechanism of adaptive and acquired resistance to targeted therapy in melanoma. Here, we show that the anti-fibrotic drug nintedanib is active to normalize the fibrous ECM network, enhance the efficacy of MAPK-targeted therapy, and delay tumor relapse in a preclinical model of melanoma. Acquisition of this resistant phenotype and its reversion by nintedanib pointed to miR-143/-145 pro-fibrotic cluster as a driver of this mesenchymal-like phenotype. Upregulation of the miR-143/-145 cluster under BRAFi/MAPKi therapy was observed in melanoma cells in vitro and in vivo and was associated with an invasive/undifferentiated profile. The 2 mature miRNAs generated from this cluster, miR-143-3p and miR-145-5p, collaborated to mediate transition toward a drug-resistant undifferentiated mesenchymal-like state by targeting Fascin actin-bundling protein 1 (FSCN1), modulating the dynamic crosstalk between the actin cytoskeleton and the ECM through the regulation of focal adhesion dynamics and mechanotransduction pathways. Our study brings insights into a novel miRNA-mediated regulatory network that contributes to non-genetic adaptive drug resistance and provides proof of principle that preventing MAPKi-induced pro-fibrotic stromal response is a viable therapeutic opportunity for patients on targeted therapy.
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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.