ArticleCancer research2008
Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
99 citing papers in PubMed, 191 citations in OpenAlex.
- Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy.Clinical proteomics · 2026Article
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- KRAS Inhibition in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2026Review
- A Novel Solution-Blow-Spinning Device Cosprays Autologous Skin Cell Suspensions and Polymer in the Treatment of Full Thickness Wounds in a Murine Model.The Journal of surgical research · 2025Article
- A web portal for exploring kinase-substrate interactions.NPJ systems biology and applications · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- AKT2 Loss Impairs BRAF-Mutant Melanoma Metastasis.Cancers · 2023Article
- Exploring the Complex and Multifaceted Interplay between Melanoma Cells and the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Article
- Targeting WEE1/AKT Restores p53-Dependent Natural Killer-Cell Activation to Induce Immune Checkpoint Blockade Responses in "Cold" Melanoma.Cancer immunology research · 2022Article
- Review
- Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape.Pharmaceutics · 2021Review
- Targeting effector pathways in RAC1Small GTPases · 2021Article
- Autophagy is induced in human keratinocytes during human papillomavirus 11 pseudovirion entry.Aging · 2020Article
- Review of PIP2 in Cellular Signaling, Functions and Diseases.International journal of molecular sciences · 2020Review
- Decoding the Role of CD271 in Melanoma.Cancers · 2020Review
- Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2020Article
- Regulatory mechanisms mediated by peroxisome proliferator-activated receptor-β/δ in skin cancer.Molecular carcinogenesis · 2019Review
- Molecular background of skin melanoma development and progression: therapeutic implications.Postepy dermatologii i alergologii · 2019Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
B-Raf is the most mutated gene in melanoma; however, the mechanism through which it promotes early melanomas remains uncertain. Most nevi contain activated (V600E)B-Raf but few develop into melanoma, and expression in melanocytes is inhibitory with low protein levels present in surviving cells, suggesting unknown cooperative oncogenic events are necessary for melanoma development. Because many melanomas have (V600E)B-Raf and active Akt3, it is possible that these proteins cooperatively facilitate melanocyte transformation. In this study, Akt3 is shown to phosphorylate (V600E)B-Raf to lower its activity as well as that of the downstream mitogen-activated protein kinase (MAPK) pathway to levels promoting early melanoma development. Expression of active Akt3 in early melanoma cells containing (V600E)B-Raf reduced MAPK signaling and promoted anchorage-independent growth. Furthermore, expression of both (V600E)B-Raf and active Akt3 in melanocytes promoted a transformed phenotype. Mechanistically, aberrant Akt3 activity in early melanomas serves to phosphorylate Ser(364) and Ser(428) on (V600E)B-Raf to reduce activity of (V600E)B-Raf to levels that promote rather than inhibit proliferation, which aids melanocytic transformation. Inhibition of (V600E)B-Raf or Akt3 in advanced melanoma cells in which both pathways were active reduced anchorage-independent growth and tumor development in a cooperatively acting manner. Inhibition of Akt3 alone in these cells led to increased MAPK signaling. In summary, these results suggest that activating B-Raf mutations initially promote nevi development, but the resulting high, intense activation of the MAPK pathway inhibits further tumor progression requiring Akt3 activation to bypass this barrier and aid melanoma development.
Indexed as
Identifiers
What OpenQuestion holds
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.