ArticleMatrix biology : journal of the International Society for Matrix Biology2015
The BRAF(V600E) inhibitor, PLX4032, increases type I collagen synthesis in melanoma cells.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Therapy-Induced ECM Remodeling Creates a Transient Immune Barrier in Residual Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting collagen to optimize cancer immunotherapy.Experimental hematology & oncology · 2025Review
- The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.International journal of molecular sciences · 2025Review
- Normal and melanoma skin visualized, quantified and compared by in vivo photoacoustic imaging.Photoacoustics · 2025Article
- Impact of Renin-Angiotensin System Inhibitors on Disease Characteristics in Patients with Localized Prostate Cancer Treated with Radical Prostatectomy: A European Association of Urology Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study.European urology open science · 2024Article
- The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance.Oncogenesis · 2023Review
- The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting TGF-β signal transduction for fibrosis and cancer therapy.Molecular cancer · 2022Review
- Impact of Collagen Triple Helix Structure on Melanoma Cell Invadopodia Formation and Matrix Degradation upon BRAF Inhibitor Treatment.Advanced healthcare materials · 2022Article
- Targeting Discoidin Domain Receptors DDR1 and DDR2 overcomes matrix-mediated tumor cell adaptation and tolerance to BRAF-targeted therapy in melanoma.EMBO molecular medicine · 2022Article
- The Role of Extracellular Matrix Remodeling in Skin Tumor Progression and Therapeutic Resistance.Frontiers in molecular biosciences · 2022Review
- Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma.Pharmaceutics · 2021Article
- TGF-β Signaling and Resistance to Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Bad Neighborhood: Fibrotic Stroma as a New Player in Melanoma Resistance to Targeted Therapies.Cancers · 2020Review
- Reciprocal Interplay Between Fibrillar Collagens and Collagen-Binding Integrins: Implications in Cancer Progression and Metastasis.Frontiers in oncology · 2020Review
- The role of collagen in cancer: from bench to bedside.Journal of translational medicine · 2019Review
- The effects of growth hormone on therapy resistance in cancer.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices.International journal of molecular sciences · 2018Article
- Potential therapeutic targets of epithelial-mesenchymal transition in melanoma.Cancer letters · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Vertical growth phase (VGP) melanoma is frequently metastatic, a process mediated by changes in gene expression, which are directed by signal transduction pathways in the tumor cells. A prominent signaling pathway is the Ras-Raf-Mek-Erk MAPK pathway, which increases expression of genes that promote melanoma progression. Many melanomas harbor a mutation in this pathway, BRAF(V600E), which constitutively activates MAPK signaling and expression of downstream target genes that facilitate tumor progression. In BRAF(V600E) melanoma, the small molecule inhibitor, vemurafenib (PLX4032), has revolutionized therapy for melanoma by inducing rapid tumor regression. This compound down-regulates the expression of many genes. However, in this study, we document that blocking the Ras-Raf-Mek-Erk MAPK pathway, either with an ERK (PLX4032) or a MEK (U1026) signaling inhibitor, in BRAF(V600E) human and murine melanoma cell lines increases collagen synthesis in vitro and collagen deposition in vivo. Since TGFß signaling is a major mediator of collagen synthesis, we examined whether blocking TGFß signaling with a small molecule inhibitor would block this increase in collagen. However, there was minimal reduction in collagen synthesis in response to blocking TGFß signaling, suggesting additional mechanism(s), which may include activation of the p38 MAPK pathway. Presently, it is unclear whether this increased collagen synthesis and deposition in melanomas represent a therapeutic benefit or an unwanted "off target" effect of inhibiting the Ras-Raf-Erk-Mek pathway.
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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.