ArticleThe Journal of clinical investigation2021
Mutant SF3B1 promotes AKT- and NF-κB-driven mammary tumorigenesis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 44 citations in OpenAlex.
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Alternative splicing rewires breast cancer and opens therapeutic avenues.Cell communication and signaling : CCS · 2026Review
- Spliceosomal mutation drives melanoma tumorigenesis via lineage-specific RAS activation.Science advances · 2026Article
- Cancer-associated SF3B1 mutation suppresses DNA repair by disrupting the organization of nuclear actin network.Cell death & disease · 2026Article
- Distinct and convergent effects ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- SF3B1 mutation accelerates the development of CLL via activation of the mTOR pathway.JCI insight · 2025Article
- SUGP1 loss drives SF3B1 hotspot mutant missplicing in cancer.Cell reports · 2025Article
- The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
- Molecular impact of mutations in RNA splicing factors in cancer.Molecular cell · 2024Review
- Engineering Oncogenic Hotspot Mutations on SF3B1 via CRISPR-Directed PRECIS Mutagenesis.Cancer research communications · 2024Article
- GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies.Molecular cell · 2024Article
- RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.Cancer cell international · 2024Review
- Comprehensive mendelian randomization reveals atrial fibrillation-breast cancer relationship and explores common druggable targets.Frontiers in pharmacology · 2024Article
- Article
- Mutant SF3B1 promotes malignancy in PDAC.eLife · 2023Article
- Targeting alternative splicing in cancer immunotherapy.Frontiers in cell and developmental biology · 2023Review
- Polyclonal evolution of Fanconi anemia to MDS and AML revealed at single cell resolution.Experimental hematology & oncology · 2022Article
- Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells.Nature biotechnology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in the core RNA splicing factor SF3B1 are prevalent in leukemias and uveal melanoma, but hotspot SF3B1 mutations are also seen in epithelial malignancies such as breast cancer. Although hotspot mutations in SF3B1 alter hematopoietic differentiation, whether SF3B1 mutations contribute to epithelial cancer development and progression is unknown. Here, we identify that SF3B1 mutations in mammary epithelial and breast cancer cells induce a recurrent pattern of aberrant splicing leading to activation of AKT and NF-κB, enhanced cell migration, and accelerated tumorigenesis. Transcriptomic analysis of human cancer specimens, MMTV-cre Sf3b1K700E/WT mice, and isogenic mutant cell lines identified hundreds of aberrant 3' splice sites (3'ss) induced by mutant SF3B1. Consistently between mouse and human tumors, mutant SF3B1 promoted aberrant splicing (dependent on aberrant branchpoints as well as pyrimidines downstream of the cryptic 3'ss) and consequent suppression of PPP2R5A and MAP3K7, critical negative regulators of AKT and NF-κB. Coordinate activation of NF-κB and AKT signaling was observed in the knockin models, leading to accelerated cell migration and tumor development in combination with mutant PIK3CA but also hypersensitizing cells to AKT kinase inhibitors. These data identify hotspot mutations in SF3B1 as an important contributor to breast tumorigenesis and reveal unique vulnerabilities in cancers harboring them.
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.