ArticleThe Journal of biological chemistry2015
Fibroblast-derived neuregulin 1 promotes compensatory ErbB3 receptor signaling in mutant BRAF melanoma.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- From HPV infection to cervical precancer: Molecular mechanisms, immune microenvironment and emerging technologies.Cellular and molecular life sciences : CMLS · 2026Review
- Targeting Cancer-Associated Fibroblasts in Prostate Cancer: Recent Advances and Therapeutic Opportunities.Cancers · 2025Review
- Elevated Transglutaminase-2 in SOX10-Deficient Melanoma Promotes Tumor Onset and Decreases Intratumoral CD4+ T Cells.Cancer research · 2025Article
- Patterns and Processes of Genomic Evolution Inferred From the Ten Smallest Vertebrate Genomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.International journal of molecular sciences · 2025Review
- Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis.Cancer & metabolism · 2025Article
- Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials.Molecular cancer · 2023Review
- MacroH2A restricts inflammatory gene expression in melanoma cancer-associated fibroblasts by coordinating chromatin looping.Nature cell biology · 2023Article
- Review
- Single-cell dissection of cellular and molecular features underlying human cervical squamous cell carcinoma initiation and progression.Science advances · 2023Article
- Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors.Molecular cancer · 2022Article
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts.Cell communication and signaling : CCS · 2022Article
- The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery.Cancers · 2022Review
- Review
- Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma.Frontiers in oncology · 2022Article
- Neratinib kills B-RAF V600E melanoma via ROS-dependent autophagosome formation and death receptor signaling.Pigment cell & melanoma research · 2022Article
- Genetic alteration of Chinese patients with rectal mucosal melanoma.BMC cancer · 2021Article
- Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy.International journal of molecular sciences · 2021Review
- Identification of Potential BRAF Inhibitor Joint Therapy Targets in PTC based on WGCAN and DCGA.Journal of Cancer · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Rapidly accelerated fibrosarcoma (RAF) inhibitors are first-line treatments for patients harboring V600E/K mutant BRAF melanoma. Although RAF inhibitors produce high response rates, the degree of tumor regression is heterogeneous. Compensatory/adaptive responses to targeted inhibitors are frequently initiated by the activation of growth factor receptor tyrosine kinases, including ErbB3, and factors from the tumor microenvironment may play an important role. We have shown previously that mutant v-raf murine sarcoma viral oncogene homolog B1 (BRAF) melanoma cells have enhanced activation of ErbB3 following RAF inhibition. However, the source of neuregulin 1 (NRG1), the ligand for ErbB3, is unknown. In this study, we demonstrate that NRG1 is highly expressed by dermal fibroblasts and cancer-associated fibroblasts (CAFs) isolated from mutant BRAF melanomas. Conditioned medium from fibroblasts and CAFs enhanced ErbB3 pathway activation and limited RAF inhibitor cytotoxicity in V600 mutant BRAF-harboring melanomas. Targeting the ErbB3/ErbB2 pathway partially reversed the protective effects of fibroblast/CAF-derived NRG1 on cell growth properties of RAF inhibitor-treated melanoma cells. These findings support the idea that NRG1, acting in a paracrine manner, promotes resistance to RAF inhibitors and emphasize that targeting the ErbB3/ErbB2 pathway will likely improve the efficacy of RAF inhibitors for mutant BRAF melanoma patients.
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