ArticleAmerican journal of cancer research2013
Krüppel-like factor 8 promotes tumorigenic mammary stem cell induction by targeting miR-146a.
Article in American journal of cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Methylation marks breast cancer metastasis: The roles of mThe Journal of biological chemistry · 2026Review
- Kruppel like factor 12 gene regulates ovarian granulosa cells proliferation and apoptosis via the PI3K/Akt signaling pathway.BMC veterinary research · 2026Article
- Implications of Krüppel-like factor signaling in neuroinflammation for neurodegenerative diseases.American journal of translational research · 2025Review
- Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance.Stem cell reviews and reports · 2023Review
- The Intricate Interplay between Cancer Stem Cells and Oncogenic miRNAs in Breast Cancer Progression and Metastasis.Life (Basel, Switzerland) · 2023Review
- KLF8 promotes invasive outgrowth of breast cancer by inducing filopodium-like protrusions via CXCR4.American journal of translational research · 2022Article
- Epigenetic Regulation of Breast Cancer Stem Cells Contributing to Carcinogenesis and Therapeutic Implications.International journal of molecular sciences · 2021Review
- MicroRNA Regulation of Breast Cancer Stemness.International journal of molecular sciences · 2021Review
- Comprehensive Analysis of Correlations in the Expression of miRNA Genes and Immune Checkpoint Genes in Bladder Cancer Cells.International journal of molecular sciences · 2021Article
- Sensitization of breast cancer to Herceptin by redox active nanoparticles.American journal of cancer research · 2021Article
- MiRNA-146a/AKT/β-Catenin Activation Regulates Cancer Stem Cell Phenotype in Oral Squamous Cell Carcinoma by Targeting CD24.Frontiers in oncology · 2021Article
- Role of krüppel-like factor 8 for therapeutic drug-resistant multi-organ metastasis of breast cancer.American journal of cancer research · 2021Article
- Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology.International journal of molecular sciences · 2020Review
- A SNP of miR-146a is involved in bladder cancer relapse by affecting the function of bladder cancer stem cells via the miR-146a signallings.Journal of cellular and molecular medicine · 2020Article
- O-GlcNAc Transferase Regulates Cancer Stem-like Potential of Breast Cancer Cells.Molecular cancer research : MCR · 2020Article
- MicroRNAs, a Promising Target for Breast Cancer Stem Cells.Molecular diagnosis & therapy · 2020Review
- Molecular alterations in non-functioning pituitary adenomas.Cancer biomarkers : section A of Disease markers · 2020Article
- Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis.International journal of medical sciences · 2020Article
- MicroRNAs, a subpopulation of regulators, are involved in breast cancer progression through regulating breast cancer stem cells.Oncology letters · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The properties of stem cells can be induced during the epithelial to mesenchymal transition (EMT). The responsible molecular mechanisms, however, remain largely undefined. Here we report the identification of the microRNA-146a (miR-146a) as a common target of Krüppel-like factor 8 (KLF8) and TGF-β, both of which are known EMT-inducers. Upon KLF8 overexpression or TGF-β treatment, a significant portion of the MCF-10A cells gained stem cell traits as demonstrated by an increased expression of CD44(high)/CD24low, activity of aldehyde dehydrogenase (ALDH), mammosphere formation and chemoresistance. Along with this change, the expression of miR-146a was highly upregulated in the cells. Importantly, we found that miR-146a was aberrantly co-overexpressed with KLF8 in a panel of invasive human breast cancer cell lines. Ectopic expression of KLF8 failed to induce the stem cell traits in the MCF-10A cells if the cells were pre-treated with miR-146a inhibitor, whereas overexpression of miR-146a in the MCF-10A cells alone was sufficient to induce the stem cell traits. Co-staining and luciferase reporter analyses indicated that miR-146a targets the 3'-UTR of the Notch signaling inhibitor NUMB for translational inhibition. Overexpression of KLF8 dramatically potentiated the tumorigenecity of MCF-10A cells expressing the H-Ras oncogene, which was accompanied by a loss of NUMB expression in the tumors. Taken together, this study identifies a novel role and mechanism for KLF8 in inducing pro-tumorigenic mammary stem cells via miR-146a potentially by activating Notch signaling. This mechanism could be exploited as a therapeutic target against drug resistance of breast cancer.
Indexed as
Identifiers
23977446PMC3744016W168414953What OpenQuestion holds
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.