ArticleActa pharmacologica Sinica2019
KLF4 functions as an oncogene in promoting cancer stem cell-like characteristics in osteosarcoma cells.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 123 citations in OpenAlex.
- Targeting Lung Cancer Stem Cells with Trimebutine: Synergistic Antitumor Activity in Combination with Cisplatin.International journal of molecular sciences · 2026Article
- Targeting FOXM1 regulates metabolic signatures through ROS-dependent JNK/Bmi1/Skp2 axis in human cutaneous T-cell lymphoma.Cell death & disease · 2026Article
- Dihydroartemisinin inhibits metastatic potential and cancer stemness by modulating the miR-200b-BMI-1/VEGF-A axis in ovarian cancer.Experimental & molecular medicine · 2025Article
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- Transcriptomic Comparisons of Somatic and Cancer Stem Cells.Biomedicines · 2025Review
- 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
- COL12A1 Promotes Osteosarcoma Progression via the FAK/PI3K/AKT/mTOR Pathway.Current molecular medicine · 2025Article
- FOSL1 promotes stem cell‑like characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.International journal of molecular medicine · 2024Article
- Multi-omics analysis unveils the predictive value of IGF2BP3/SPHK1 signaling in cancer stem cells for prognosis and immunotherapeutic response in muscle-invasive bladder cancer.Journal of translational medicine · 2024Article
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression.Scientific reports · 2024Article
- EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells.International journal of molecular sciences · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024Review
- Cancer cell plasticity, stem cell factors, and therapy resistance: how are they linked?Cancer metastasis reviews · 2024Review
- USP40 promotes hepatocellular carcinoma cell proliferation, migration and stemness by deubiquitinating and stabilizing Claudin1.Biology direct · 2024Article
- Review
- Exploring the heterogeneity of osteosarcoma cell characteristics and metabolic states and their association with clinical prognosis.Frontiers in immunology · 2024Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite more effective chemotherapy combined with limb-salvage surgery for the osteosarcoma treatment, survival rates for osteosarcoma patients have stagnated over the past three decades due to the poor prognosis. Osteosarcoma cancer stem cells (OSCs) are responsible for the growth and metastasis of osteosarcoma. The existence of OSCs offers a theoretical explanation for therapeutic failures including tumor recurrence, metastasis, and drug resistance. Understanding the pathways that regulate properties of OSCs may shed light on mechanisms that lead to osteosarcoma and suggest better modes of treatment. In this study, we showed that the expression level of Kruppel-like factor 4 (KLF4) is highly associated with human osteosarcoma cancer stemness. KLF4-overexpressed osteosarcoma cells displayed characteristics of OSCs: increased sphere-forming potential, enhanced levels of stemness-associated genes, great chemoresistance to adriamycin and CDDP, as well as more metastasis potential. Inversely, KLF4 knockdown could reduce colony formation in vitro and inhibit tumorigenesis in vivo, supporting an oncogenic role for KLF4 in osteosarcoma pathogenesis. Furthermore, KLF4 was shown to activate the p38 MAPK signaling pathway to promote cancer stemness. Altogether, our studies uncover an essential role for KLF4 in regulation of OSCs and identify KLF4-p38 MAPK axis as a potential therapeutic target for osteosarcoma treatment.
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