ArticlePigment cell & melanoma research2008
Oncogenic BRAF(V600E) inhibits BIM expression to promote melanoma cell survival.
Article in Pigment cell & melanoma research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 116 citations in OpenAlex.
- Trial
- Identification and characterization of BRAF⇔TP53 interactions in melanoma.Cell reports · 2026Article
- RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.Cancer immunology research · 2026Article
- Programmed cell death evasion in BRAF V600E-driven primary CNS tumors and thyroid cancer brain metastases.Frontiers in neurology · 2026Review
- TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Regorafenib induces Bim-mediated intrinsic apoptosis by blocking AKT-mediated FOXO3a nuclear export.Cell death discovery · 2023Article
- Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics.Cancer discovery · 2022Review
- Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma.Journal of personalized medicine · 2021Review
- Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma.Cancers · 2020Article
- Inhibition of MEK1/2 Forestalls the Onset of Acquired Resistance to Entrectinib in Multiple Models of NTRK1-Driven Cancer.Cell reports · 2020Article
- FGF2 Induces Resistance to Nilotinib through MAPK Pathway Activation in KIT Mutated Melanoma.Cancers · 2020Article
- Non-Apoptotic Cell Death Signaling Pathways in Melanoma.International journal of molecular sciences · 2020Review
- Translational pathology, genomics and the development of systemic therapies for acral melanoma.Seminars in cancer biology · 2020Review
- The Macro-Autophagy-Related Protein Beclin-1 Immunohistochemical Expression Correlates With Tumor Cell Type and Clinical Behavior of Uveal Melanoma.Frontiers in oncology · 2020Article
- Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies.Nature communications · 2019Article
- HDAC8 Regulates a Stress Response Pathway in Melanoma to Mediate Escape from BRAF Inhibitor Therapy.Cancer research · 2019Article
- Countering TRAIL Resistance in Melanoma.Cancers · 2019Review
- The BRAF-inhibitor PLX4720 inhibits CXCL8 secretion in BRAFV600E mutated and normal thyroid cells: a further anti-cancer effect of BRAF-inhibitors.Scientific reports · 2019Article
- Mechanism of action of the third generation benzopyrans and evaluation of their broad anti-cancer activity in vitro and in vivo.Scientific reports · 2018Article
- Mutant BRAF Upregulates MCL-1 to Confer Apoptosis Resistance that Is Reversed by MCL-1 Antagonism and Cobimetinib in Colorectal Cancer.Molecular cancer therapeutics · 2016Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Somatic activating mutations of BRAF are the earliest and most common genetic abnormality detected in the genesis of human melanoma. However, the mechanism(s) by which activated BRAF promotes melanoma cell cycle progression and/or survival remain unclear. Here we demonstrate that expression of BIM, a pro-apoptotic member of the BCL-2 family, is inhibited by BRAF-->MEK-->ERK signaling in mouse and human melanocytes and in human melanoma cells. Trophic factor deprivation of melanocytes leads to elevated BIM expression. However, re-addition of trophic factors or activation of a conditional form of BRAF(V600E) leads to rapid inhibition of BIM expression. In both cases, inhibition of BIM expression was dependent on the activity of MEK1/2 and the proteasome. Consistent with these observations, pharmacological inhibition of BRAF(V600E) or MEK1/2 in human melanoma cells (using PLX4720 and CI-1040 respectively) led to a striking elevation of BIM expression. Re-activation of BRAF-->MEK-->ERK signaling led to phosphorylation of BIM-EL on serine 69 and its subsequent degradation. Interestingly, endogenous expression of BIM in melanoma cells was insufficient to induce apoptosis unless combined with serum deprivation. Under these circumstances, inhibition of BIM expression by RNA interference provided partial protection from apoptosis. These data suggest that regulation of BIM expression by BRAF-->MEK-->ERK signaling is one mechanism by which oncogenic BRAF(V600E) can influence the aberrant physiology of melanoma cells.
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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.