ArticleOncotarget2016
Inhibition of SP1 by the mithramycin analog EC-8042 efficiently targets tumor initiating cells in sarcoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Retroelements in thyroid cancer: epigenetic plasticity, dedifferentiation, and therapeutic opportunities.Reviews in endocrine & metabolic disorders · 2026Review
- Proteomics analysis of human mesenchymal stromal/stem cell sarcomagenesis model identifies ALDH1A3 and CD99 as potential targets in the transformation process.BMC biology · 2026Article
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Mithramycin targets head and neck cancer stem cells by inhibiting Sp1 and UFMylation.Cancer cell international · 2024Article
- Docking and molecular dynamic simulations of Mithramycin-A and Tolfenamic acid against Sp1 and survivin.Process biochemistry (Barking, London, England) · 2024Article
- Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy.International journal of molecular sciences · 2024Review
- Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.Current issues in molecular biology · 2023Review
- Article
- Differential Impact of Random GC Tetrad Binding and Chromatin Events on Transcriptional Inhibition by Olivomycin A.International journal of molecular sciences · 2022Article
- Addressing Doxorubicin Resistance in Bone Sarcomas Using Novel Drug-Resistant Models.International journal of molecular sciences · 2022Article
- Mithramycin delivery systems to develop effective therapies in sarcomas.Journal of nanobiotechnology · 2021Article
- TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma.Haematologica · 2021Article
- Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas.Journal of clinical medicine · 2021Article
- Osteosarcoma tissue-engineered model challenges oxidative stress therapy revealing promoted cancer stem cell properties.Free radical biology & medicine · 2021Article
- Review
- Combinatorial Strategies to Target Molecular and Signaling Pathways to Disarm Cancer Stem Cells.Frontiers in oncology · 2021Review
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
- Mithramycin A and Mithralog EC-8042 Inhibit SETDB1 Expression and Its Oncogenic Activity in Malignant Melanoma.Molecular therapy oncolytics · 2020Article
- Heterologous reconstitution of the biosynthesis pathway for 4-demethyl-premithramycinone, the aglycon of antitumor polyketide mithramycin.Microbial cell factories · 2020Article
- Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor initiating cells (TICs), responsible for tumor initiation, and cancer stem cells (CSCs), responsible for tumor expansion and propagation, are often resistant to chemotherapeutic agents. To find therapeutic targets against sarcoma initiating and propagating cells we used models of myxoid liposarcoma (MLS) and undifferentiated pleomorphic sarcoma (UPS) developed from human mesenchymal stromal/stem cells (hMSCs), which constitute the most likely cell-of-origin for sarcoma. We found that SP1-mediated transcription was among the most significantly altered signaling. To inhibit SP1 activity, we used EC-8042, a mithramycin (MTM) analog (mithralog) with enhanced anti-tumor activity and highly improved safety. EC-8042 inhibited the growth of TIC cultures, induced cell cycle arrest and apoptosis and upregulated the adipogenic factor CEBPα. SP1 knockdown was able to mimic the anti-proliferative effects induced by EC-8042. Importantly, EC-8042 was not recognized as a substrate by several ABC efflux pumps involved in drug resistance, and, opposite to the chemotherapeutic drug doxorubicin, repressed the expression of many genes responsible for the TIC/CSC phenotype, including SOX2, C-MYC, NOTCH1 and NFκB1. Accordingly, EC-8042, but not doxorubicin, efficiently reduced the survival of CSC-enriched tumorsphere sarcoma cultures. In vivo, EC-8042 induced a profound inhibition of tumor growth associated to a strong reduction of the mitotic index and the induction of adipogenic differentiation and senescence. Finally, EC-8042 reduced the ability of tumor cells to reinitiate tumor growth. These data suggest that EC-8042 could constitute an effective treatment against both TIC and CSC subpopulations in sarcoma.
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