ArticleProceedings of the National Academy of Sciences of the United States of America2014
Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk.International journal of cancer · 2020Pooled it
- Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer.Molecular & cellular proteomics : MCP · 2015Trial
- Systematic Analysis of MRTFB Phosphoproteomic Datasets Reveals Co-Regulated Kinase Networks and Co-Occurring Phosphosites Associated with the Actin Cytoskeleton Pathway.Current issues in molecular biology · 2026Article
- First Glance at Myeloid Leukaemia Factor 2 in Cardiomyocytes.Journal of cardiovascular development and disease · 2025Article
- PIM3-mediated phosphorylation stabilizes myeloid leukemia factor 2 to promote metastasis in osteosarcoma.The Journal of clinical investigation · 2025Article
- RPL39 Was Associated With Sex Differences in Pulmonary Arterial Hypertension.Canadian respiratory journal · 2025Article
- NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.Nature communications · 2024Article
- CPSF4-mediated regulation of alternative splicing of HMG20B facilitates the progression of triple-negative breast cancer.Journal of translational medicine · 2024Article
- Regulation and Pharmacology of the Cyclic GMP and Nitric Oxide Pathway in Embryonic and Adult Stem Cells.Cells · 2024Review
- Ribosome biogenesis and ribosomal proteins in cancer stem cells: a new therapeutic prospect.Molecular biology reports · 2024Review
- Article
- TAF2, within the TFIID complex, regulates the expression of a subset of protein-coding genes.Cell death discovery · 2024Article
- In Vivo Investigation of the Effect of Dietary Acrylamide and Evaluation of Its Clinical Relevance in Colon Cancer.Toxics · 2023Article
- Potential Candidate Genes for Therapeutic Targeting in Chronic Myeloid Leukemia: A Pilot Study.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- hapln1aNature communications · 2023Article
- Targeting Nitric Oxide: Say NO to Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Chronic Exposure to Nitric Oxide Induces P53 Mutations and Malignant-like Features in Human Breast Epithelial Cells.Biomolecules · 2023Article
- GAPDH: unveiling its impact as a key hypoxia-related player in head and neck squamous cell carcinoma tumor progression, prognosis, and therapeutic potential.American journal of cancer research · 2023Article
- Proteomic profiling of urinary extracellular vesicles differentiates breast cancer patients from healthy women.PloS one · 2023Article
15 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
23 authors at 8 institutions in 4 countries.
Funding
Abstract
We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.
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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.