ArticleThe Journal of investigative dermatology2015
NF-κB Regulation of c-FLIP Promotes TNFα-Mediated RAF Inhibitor Resistance in Melanoma.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- AC3Medical oncology (Northwood, London, England) · 2026Article
- Biological Functions and Clinical Implications of CFLAR: From Cell Death Mechanisms to Therapeutic Targeting in Immune Regulation.Journal of inflammation research · 2025Review
- Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors inScience signaling · 2024Article
- Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.Viruses · 2022Review
- X-linked inhibitor of apoptosis protein (XIAP) predicts disease-free survival inFrontiers in endocrinology · 2022Article
- Signal pathways of melanoma and targeted therapy.Signal transduction and targeted therapy · 2021Review
- Review
- Ultraviolet Radiation and Chronic Inflammation-Molecules and Mechanisms Involved in Skin Carcinogenesis: A Narrative Review.Life (Basel, Switzerland) · 2021Review
- Beyond K48 and K63: non-canonical protein ubiquitination.Cellular & molecular biology letters · 2021Review
- 17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines.International journal of molecular sciences · 2020Article
- Inhibitors of HSP90 in melanoma.Apoptosis : an international journal on programmed cell death · 2020Review
- K27-linked ubiquitination of BRAF by ITCH engages cytokine response to maintain MEK-ERK signaling.Nature communications · 2019Article
- RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors.Cell death & disease · 2018Article
- Schizandrin B inhibits the cis‑DDP‑induced apoptosis of HK‑2 cells by activating ERK/NF‑κB signaling to regulate the expression of survivin.International journal of molecular medicine · 2018Article
- Systemic network analysis identifies XIAP and IκBα as potential drug targets in TRAIL resistant BRAF mutated melanoma.NPJ systems biology and applications · 2018Article
- Methylglyoxal-induced apoptosis is dependent on the suppression of c-FLIPJournal of cellular and molecular medicine · 2017Article
- MALT1 promotes melanoma progression through JNK/c-Jun signaling.Oncogenesis · 2017Article
- RIP-1/c-FLIPL Induce Hepatic Cancer Cell Apoptosis Through Regulating Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL).Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Chronic Inflammation in Skin Malignancies.Journal of molecular signaling · 2016Review
- Parthenolide induces MITF-M downregulation and senescence in patient-derived MITF-M(high) melanoma cell populations.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Targeted inhibitors elicit heterogeneous clinical responses in genetically stratified groups of patients. Although most studies focus on tumor intrinsic properties, factors in the tumor microenvironment were recently found to modulate the response to inhibitors. Here, we show that in cutaneous BRAF V600E melanoma, the cytokine tumor necrosis factor-α (TNFα) blocks RAF inhibitor-induced apoptosis via activation of NF-κB. Several NF-κB-dependent factors are upregulated following TNFα and RAF inhibitor treatment. Of these factors, we show that death receptor inhibitor cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) is required for TNFα-induced protection against RAF inhibitor. Overexpression of c-FLIP_S or c-FLIP_L isoform decreased RAF inhibitor-induced apoptosis in the absence of TNFα. Importantly, targeting NF-κB enhances response to RAF inhibitor in vitro and in vivo. Together, our results show mechanistic evidence for cytokine-mediated resistance to RAF inhibitor and provide a preclinical rationale for the strategy of cotargeting the RAF/MEK/ERK1/2 pathway and the TNFα/NF-κB axis to treat mutant BRAF melanomas.
Indexed as
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What OpenQuestion holds
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.