ArticleStem cell reports2017
Inhibition of KLF4 by Statins Reverses Adriamycin-Induced Metastasis and Cancer Stemness in Osteosarcoma Cells.
Article in Stem cell reports, 2017. 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 33 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.
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
33 citing papers in PubMed, 64 citations in OpenAlex.
- Nrf2 Drives Epigenetic Reprogramming and Acts as the Master Regulator of KLF4 Expression and Activity in Arsenic-Induced Transformation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PDK1-dependent metabolic reprogramming regulates stemness and tumorigenicity of osteosarcoma stem cells through ATF3.Cell death & disease · 2025Article
- Modulating Cancer Stem Cell Characteristics in CD133+ Melanoma Cells through Hif1α, KLF4, and SHH Silencing.ACS omega · 2025Article
- Arsenic disrupts H3K9me3 and H3K27me3 balance by biasing PRC2.1 and PRC2.2 activity via PALI1 inhibition in carcinogenesis.International journal of biological sciences · 2025Article
- Dysregulation of the p53 pathway provides a therapeutic target in aggressive pediatric sarcomas with stem-like traits.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Decoding Chemotherapy Resistance of Undifferentiated Pleomorphic Sarcoma at the Single Cell Resolution: A Case Report.Journal of clinical medicine · 2024Article
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024Review
- Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma.Communications biology · 2023Article
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers.International journal of molecular sciences · 2023Review
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- Role of O-GlcNAcylation on cancer stem cells: Connecting nutrient sensing to cell plasticity.Advances in cancer research · 2023Review
- Kruppel-like Factors in Skeletal Physiology and Pathologies.International journal of molecular sciences · 2022Review
- Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers.Cancers · 2022Review
- Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- KLF4 Induces Mesenchymal-Epithelial Transition (MET) by Suppressing Multiple EMT-Inducing Transcription Factors.Cancers · 2021Article
- Article
- Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.Cancers · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adriamycin-based combination chemotherapy is the standard first-line treatment for osteosarcoma, but tumor recurrence and metastasis occurs in most cases. Recent evidence suggests that microenvironmental stress such as chemotherapy can lead to the enrichment of cancer stem cells (CSCs), which result in cancer metastasis, recurrence, and drug resistance. However, the exact mechanisms underlying this phenomenon and how to target CSCs are still open questions. Herein, we report that Adriamycin treatment induces a stem-like phenotype and promotes metastatic potential in osteosarcoma cells through upregulating KLF4. KLF4 knockdown blocks Adriamycin-induced stemness phenotype and metastasis capacity. We further screen that statins remarkably reverse Adriamycin-induced CSC properties and metastasis by downregulating KLF4. Most strikingly, simvastatin severely impaired Adriamycin-enhanced tumorigenesis of KHOS/NP cells in vivo. These data suggest that Adriamycin-based chemotherapeutics may simulate CSCs through activation of KLF4 signaling and that selective inhibition of KLF4 with statins should be considered in the development of osteosarcoma therapeutics.
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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.