ArticleOncogene2016
Oncogene-induced senescence underlies the mutual exclusive nature of oncogenic KRAS and BRAF.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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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.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- RAS pathway mutations orchestrate chromatin reconfiguration and transcriptional rewiring in colorectal cancer.Cell communication and signaling : CCS · 2026Article
- Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.Acta oncologica (Stockholm, Sweden) · 2026Article
- Empowering Inference of Epistasis on the Basis of Mutual Exclusivity, Co-Occurrence, Functional Antagonism and Synergy in ERK-Pathway Oncogenes.International journal of cancer · 2026Article
- Variant-Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs.International journal of cancer · 2026Article
- MAPK-driven MYC/p21 axis controls senescence bypass and BCL-XL dependence in vincristine-resistant rhabdomyosarcoma.iScience · 2026Article
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- BRAF and RAS mutations in Vietnamese patients with ameloblastoma.BMC oral health · 2026Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Variable thresholds for phosphorylation targets of the ERK signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- BRAF inhibition increases TGFβ2 production and stimulates metastasis in mice with endogenous BRAFProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- The atypical KRASMolecular oncology · 2025Article
- Homologous recombination deficiency among patients with germline or somatic non-BRCA1/2 homologous recombination repair gene variations.NPJ precision oncology · 2025Article
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- Multiomics Identifies Potential Molecular Profiles Associated With Outcomes After BRAF-Targeted Therapy in Patients With BRAF V600E-Mutated Advanced Solid Tumors.JCO precision oncology · 2025Article
- Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- RNF2 promotes chondrosarcoma progression by regulating ubiquitination and degradation of CBX7.Cancer & metabolism · 2024Article
- Super multiple primary lung cancers harbor high-frequency BRAF and low-frequency EGFR mutations in the MAPK pathway.NPJ precision oncology · 2024Article
- Review
2 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS and BRAF are among the most commonly mutated oncogenes in human cancer that contribute to tumorigenesis in both distinct and overlapping tissues. However, KRAS and BRAF mutations are mutually exclusive; they never occur in the same tumor cell. The reason for the mutual exclusivity is unknown, but there are several possibilities. The two mutations could be functionally redundant and not create a selective advantage to tumor cells. Alternatively, they could be deleterious for the tumor cell and induce apoptosis or senescence. To distinguish between these possibilities, we activated the expression of BRAF(V600E) and KRAS(G12D) from their endogenous promoters in mouse lungs. Although the tumor-forming ability of BRAF(V600E) was higher than KRAS(G12D), KRAS(G12D) tumors were larger and more advanced. Coactivation of BRAF(V600E) and KRAS(G12D) markedly reduced lung tumor numbers and overall tumor burden compared with activation of BRAF(V600E) alone. Moreover, several tumors expressed only one oncogene, suggesting negative selection against expression of both. Similarly, expression of both oncogenes in mouse embryonic fibroblasts essentially stopped proliferation. The expression of both oncogenes hyperactivated the MEK-ERK-cyclin D pathway but reduced proliferation by increasing the production of p15, p16 and p19 proteins encoded by the Ink4/Arf locus and thereby increased senescence-associated β-galactosidase-positive cells. The data suggest that coexpression of BRAF(V600E) and KRAS(G12D) in early tumorigenesis leads to negative selection due to oncogene-induced senescence.
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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.