ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
C-Raf is associated with disease progression and cell proliferation in a subset of melanomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Lidocaine enhances antitumor effects of sorafenib and GW5074 in colorectal cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.Journal for immunotherapy of cancer · 2024Article
- Activation of MAP Kinase Pathway by Polyisoprenylated Cysteinyl Amide Inhibitors Causes Apoptosis and Disrupts Breast Cancer Cell Invasion.Biomedicines · 2024Article
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- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- PHI-1, an Endogenous Inhibitor Protein for Protein Phosphatase-1 and a Pan-Cancer Marker, Regulates Raf-1 Proteostasis.Biomolecules · 2023Article
- 2-Aminobenzothiazoles in anticancer drug design and discovery.Bioorganic chemistry · 2023Review
- Recognition of BRAF by CDC37 and Re-Evaluation of the Activation Mechanism for the Class 2 BRAF-L597R Mutant.Biomolecules · 2022Article
- Harnessing the polyamine transport system to treat BRAF inhibitor-resistant melanoma.Cancer biology & therapy · 2021Article
- Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases.Journal of neuro-oncology · 2021Article
- Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis.Pigment cell & melanoma research · 2021Review
- Article
- Review
- PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Raf kinase inhibitor RKIP inhibits MDA-9/syntenin-mediated metastasis in melanoma.Cancer research · 2012Article
- Upregulation of MAPK pathway is associated with survival in castrate-resistant prostate cancer.British journal of cancer · 2011Article
- In vitro studies of dasatinib, its targets and predictors of sensitivity.Pigment cell & melanoma research · 2011Article
- Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health.Oncotarget · 2011Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeRaf-kinases include three major isoforms. Although the role of B-Raf in melanoma is well established, little is known about C-Raf. We studied effects of C-Raf knockdown in vitro and assessed expression of C-Raf in a large cohort of melanomas and nevi. EXPERIMENTAL
designUsing specific siRNAs, we knocked down C-Raf expression, and determined the effect on viability, MAP extracellular signal-regulated kinase (ERK)/ERK kinase signaling, and apoptosis in seven melanoma cell lines. We determined the IC(50) of the C-Raf inhibitors sorafenib and GW5074, and studied the effects of GW5074 on cell signaling. Using an automated method to measure in situ protein expression, we quantified C-Raf expression in 263 nevi and 523 melanomas.
resultsC-Raf was knocked down in three cell lines with detectable phospho-C-Raf, resulting in decreased viability in two of the three (YULAC and YUROB). This resulted in decreased Bcl-2 expression and phospho-Bad cleavage, without affecting phospho-MEK and phospho-ERK. Sensitivity to sorafenib and GW5074 varied. GW5074 inhibited mitogen-activated protein kinase signaling without Bcl-2 and phospho-Bad down-regulation. C-Raf was highly expressed in melanomas compared with nevi (P < 0.0001), and no nevi had high C-Raf expression. C-Raf expression was higher in metastatic than primary specimens (P = 0.0225).
conclusionsC-Raf siRNA knock-down results in decreased viability of YULAC (B-Raf(V600K)) and YUROB (B-Raf(WT)) melanoma cells, likely mediated by Bcl-2 inhibition rather than mitogen-activated protein kinase inhibition. Cotargeting C-Raf and parallel pathways might be an effective therapeutic approach for melanoma. C-Raf expression is up-regulated in a subset of melanomas but not in nevi, suggesting that it might be a valuable diagnostic marker and therapeutic target.
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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.