ArticleNature medicine2018
Positively selected enhancer elements endow osteosarcoma cells with metastatic competence.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 172 citations in OpenAlex.
- Sarcoma metastasis: distinct biological principles beyond the carcinoma paradigm.Cancer metastasis reviews · 2026Review
- AP1 Transcription Factor in the Regulation of the Urokinase Plasminogen Activation System.Biomolecules · 2026Review
- Generation of a comprehensive epigenomic atlas in clear cell renal cell carcinoma informs kidney cancer progression and heritability.Cell reports · 2026Article
- Genome-wide screenings identify BAP1 as a synthetic-lethality target with CDK4/6 inhibitors.Science advances · 2026Article
- Etoposide activates CD8Journal for immunotherapy of cancer · 2025Article
- HMGB3 promotes brain metastasis of lung adenocarcinoma by recruiting SSBP1 for nuclear translocation to remodel mitochondrial metabolism.Cancer communications (London, England) · 2025Article
- Therapeutic Targeting of BET Proteins in Sarcoma.Molecular cancer therapeutics · 2025Review
- Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.Nature communications · 2025Article
- Comprehensive multi-omics analysis of histone acetylation modulators identifies ASH1L as a novel aggressive marker for osteosarcoma.Discover oncology · 2025Article
- SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers.Nature communications · 2025Article
- Upregulated ATG4B predicts poor prognosis and correlates with angiogenesis in osteosarcoma.Journal of the Egyptian National Cancer Institute · 2025Article
- Application and mechanisms of targeting BRD4 in osteosarcoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- The Dynamic Landscape of the Coagulome of Metastatic Malignant Melanoma.International journal of molecular sciences · 2025Article
- Machine learning tools for deciphering the regulatory logic of enhancers in health and disease.Frontiers in genetics · 2025Review
- Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.Cancer letters · 2024Article
- Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- A useful mTORC1 signaling-related RiskScore model for the personalized treatment of osteosarcoma patients by using the bulk RNA-seq analysis.Discover oncology · 2024Article
- Intrinsic Epigenetic State of Primary Osteosarcoma Drives Metastasis.Molecular cancer research : MCR · 2024Article
- Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
26 authors at 7 institutions in 3 countries.
Funding
Abstract
Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs). Met-VELs drive coordinated waves of gene expression during metastatic colonization of the lung. Met-VELs cluster nonrandomly in the genome, indicating that activity of these enhancers and expression of their associated gene targets are positively selected. As evidence of this causal association, osteosarcoma lung metastasis is inhibited by global interruptions of Met-VEL-associated gene expression via pharmacologic BET inhibition, by knockdown of AP-1 transcription factors that occupy Met-VELs, and by knockdown or functional inhibition of individual genes activated by Met-VELs, such as that encoding coagulation factor III/tissue factor (F3). We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. These findings indicate that Met-VELs and the genes they regulate play a functional role in metastasis and may be suitable targets for antimetastatic therapies.
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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.