ReferenceID 4739
Bilirubin Restrains the Anticancer Effect of Vemurafenib on BRAF-Mutant Melanoma Cells Through ERK-MNK1 Signaling
Front Oncol
Melanoma, the most threatening cancer in the skin, has been considered to be driven by the carcinogenic RAF-MEK1/2-ERK1/2 signaling pathway. This signaling pathway is usually mainly dysregulated by mutations in BRAF or R
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Record Fields
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- Reference Id
- 4739
- Evidence Id
- 21329
- Core Evidence Id
- 21329
- Source Reference Id
- 2719
- Herb2 Reference Id
- HBREF003516
- Subject Paper Key
- HBIN018510_34222023
- Pubmed Id
- 34222023
- Doi
- 10.3389/fonc.2021.698888
- Paper Title
- Bilirubin Restrains the Anticancer Effect of Vemurafenib on BRAF-Mutant Melanoma Cells Through ERK-MNK1 Signaling
- Paper Abstract
- Melanoma, the most threatening cancer in the skin, has been considered to be driven by the carcinogenic RAF-MEK1/2-ERK1/2 signaling pathway. This signaling pathway is usually mainly dysregulated by mutations in BRAF or RAS in skin melanomas. Although inhibitors targeting mutant BRAF, such as vemurafenib, have improved the clinical outcome of melanoma patients with BRAF mutations, the efficiency of vemurafenib is limited in many patients. Here, we show that blood bilirubin in patients with BRAF-mutant melanoma treated with vemurafenib is negatively correlated with clinical outcomes. In vitro and animal experiments show that bilirubin can abrogate vemurafenib-induced growth suppression of BRAF-mutant melanoma cells. Moreover, bilirubin can remarkably rescue vemurafenib-induced apoptosis. Mechanically, the activation of ERK-MNK1 axis is required for bilirubin-induced reversal effects post vemurafenib treatment. Our findings not only demonstrate that bilirubin is an unfavorable for patients with BRAF-mutant melanoma who received vemurafenib treatment, but also uncover the underlying mechanism by which bilirubin restrains the anticancer effect of vemurafenib on BRAF-mutant melanoma cells.
- Journal
- Front Oncol
- Publish Year
- 2021
- Experiment Subject
- patient; braf-mutant melanoma cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Skin Melanomas; Vemurafenib; Melanoma; Cancer; Braf-mutant Melanoma
- Paper Title Cn
- Paper Title En
- Bilirubin Restrains the Anticancer Effect of Vemurafenib on BRAF-Mutant Melanoma Cells Through ERK-MNK1 Signaling
- Bilingual Status
- semi_complete