ArticleOncotarget2017
BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors: A Systematic Review and Meta-analysis.JAMA network open · 2019Pooled it
- CD47 promotes mitogen-activated protein kinase and epithelial-to-mesenchymal transition molecular programs to drive prometastatic phenotypes in non-small cell lung cancer.Molecular oncology · 2026Article
- GV1001 Reprograms CD47 Immune Checkpoint to Restore Macrophage Antitumor Activity in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Review
- Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy.Blood · 2025Article
- Dissecting CD47 expression in lymphoid neoplasms to inform precision immunotherapy with anti-CD47 phagocytic checkpoint blockade.Haematologica · 2025Article
- Ex vivo engineering of phagocytic signals in breast cancer cells for a whole tumor cell-based vaccine.BMC cancer · 2025Article
- Matters of the Heart: Cardiotoxicity Related to Target Therapy in Oncogene-Addicted Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Article
- NRF-1 transcription factor regulates expression of an innate immunity checkpoint, CD47, during melanomagenesis.Frontiers in immunology · 2024Article
- Management of hypertension in patients with cancer: challenges and considerations.Clinical kidney journal · 2023Review
- Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.Cell death & disease · 2023Article
- A MD Simulation Prediction for Regulation ofMolecules (Basel, Switzerland) · 2023Article
- Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension-Mechanisms and Mitigation.Hypertension (Dallas, Tex. : 1979) · 2023Review
- CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer.Frontiers of medicine · 2023Article
- Cabozantinib, Vandetanib, Pralsetinib and Selpercatinib as Treatment for Progressed Medullary Thyroid Cancer with a Main Focus on Hypertension as Adverse Effect.International journal of molecular sciences · 2023Review
- Putting the brakes on phagocytosis: "don't-eat-me" signaling in physiology and disease.EMBO reports · 2021Review
- Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients.Circulation research · 2021Review
- MITF induces escape from innate immunity in melanoma.Journal of experimental & clinical cancer research : CR · 2021Article
- CD47/SIRPα pathway mediates cancer immune escape and immunotherapy.International journal of biological sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47. The increase in CD47 expression was mediated by ERK signalling, as it was associated with rebound activation of ERK and co-knockdown of ERK1/2 by siRNA diminished upregulation of CD47 in melanoma cells after exposure to BRAF/MEK inhibitors. Furthermore, ERK1/2 knockdown also reduced the constitutive expression of CD47 in melanoma cells. We identified a DNA fragment that was enriched with the consensus binding sites for NRF-1 and was transcriptionally responsive to BRAF/MEK inhibitor treatment. Knockdown of NRF-1 inhibited the increase in CD47, indicating that NRF-1 has a critical role in transcriptional activation of CD47 by ERK signalling. Functional studies showed that melanoma cells resistant to vemurafenib were more susceptible to macrophage phagocytosis when CD47 was blocked. So these results suggest that NRF-1-mediated regulation of CD47 expression is a novel mechanism by which ERK signalling promotes the pathogenesis of melanoma, and that the combination of CD47 blockade and BRAF/MEK inhibitors may be a useful approach for improving their therapeutic efficacy.
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Registered trials
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