ArticleOncotarget2015
The c-Jun/RHOB/AKT pathway confers resistance of BRAF-mutant melanoma cells to MAPK inhibitors.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Phosphatidylserine and RhoB connect PI4P and PA metabolism to maintain plasma membrane identity.The Journal of cell biology · 2026Article
- Therapeutic Potential of Tyrosine Kinase Inhibitors in Advanced Thyroid Cancer.Current oncology reports · 2026Review
- Identification of a Highly Cooperative PROTAC Degrader Targeting GTP-Loaded KRAS(On) Alleles.Journal of the American Chemical Society · 2025Article
- Fyn inhibition by TAE684: A synergistic strategy to suppress melanoma and reverse vemurafenib resistance.Cell death & disease · 2025Article
- Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane.bioRxiv : the preprint server for biology · 2025Article
- Jun, an Oncological Foe or Friend?International journal of molecular sciences · 2025Review
- TRP-related gene signatures predict survival and the immune microenvironment in rectal cancer: a comprehensive bioinformatics study.Frontiers in immunology · 2025Article
- BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2023Review
- Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers.Endocrine-related cancer · 2022Review
- Review
- Tripartite split-GFP assay to identify selective intracellular nanobody that suppresses GTPase RHOA subfamily downstream signaling.Frontiers in immunology · 2022Article
- Irreversible JNK blockade overcomes PD-L1-mediated resistance to chemotherapy in colorectal cancer.Oncogene · 2021Article
- Review
- Innate and Adaptive Immunity Linked to Recognition of Antigens Shared by Neural Crest-Derived Tumors.Cancers · 2020Review
- Selection and Characterization of a Nanobody Biosensor of GTP-Bound RHO Activities.Antibodies (Basel, Switzerland) · 2019Article
- Identification of potential biomarkers in cervical cancer with combined public mRNA and miRNA expression microarray data analysis.Oncology letters · 2018Article
- The Dietary Supplement Chondroitin-4-Sulfate Exhibits Oncogene-Specific Pro-tumor Effects on BRAF V600E Melanoma Cells.Molecular cell · 2018Article
- RhoB: Team Oncogene or Team Tumor Suppressor?Genes · 2018Review
- High-content tripartite split-GFP cell-based assays to screen for modulators of small GTPase activation.Journal of cell science · 2018Article
- Identification of WEE1 as a target to make AKT inhibition more effective in melanoma.Cancer biology & therapy · 2018Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The response of BRAF-mutant melanoma patients to BRAF inhibitors is dramatically impaired by secondary resistances and rapid relapse. So far, the molecular mechanisms driving these resistances are not completely understood. Here, we show that, in BRAF-mutant melanoma cells, inhibition of BRAF or its target MEK induces RHOB expression by a mechanism that depends on the transcription factor c-Jun. In those cells, RHOB deficiency causes hypersensitivity to BRAF and MEK inhibitors-induced apoptosis. Supporting these results, loss of RHOB expression in metastatic melanoma tissues is associated with an increased progression-free survival of BRAF-mutant patients treated with vemurafenib. Following BRAF inhibition, RHOB activates AKT whose inhibition causes hypersensitivity of BRAF-mutant melanoma cells to BRAF inhibitors. In mice, AKT inhibition synergizes with vemurafenib to block tumor growth of BRAF-mutant metastatic melanoma. Our findings reveal that BRAF inhibition activates a c-Jun/RHOB/AKT pathway that promotes tumor cell survival and further support a role of this pathway in the resistance of melanoma to vemurafenib. Our data also highlight the importance of using RHOB tumor levels as a biomarker to predict vemurafenib patient's response and to select those that would benefit of the combination with AKT inhibitors.
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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.