ArticleThe Journal of biological chemistry2008
Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 2 of them syntheses that pooled it.
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Who cites it
254 citing papers in PubMed, 2 syntheses or guidelines pooled it, 439 citations in OpenAlex.
- Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells.Frontiers in pharmacology · 2023Pooled it
- A Systematic Review to Clarify the Prognostic Values of CD44 and CD44Frontiers in oncology · 2021Pooled it
- Article
- DCLK1 regulates stemness and IL-6/STAT3-dependent metastatic niche formation in chemoresistant ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Keratin 5 marks cancer-propagating cells sustained by an osteopontin-producing niche in high-grade serous ovarian carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Normalizing the Tumor Microenvironment: A New Frontier in Ovarian Cancer Therapy.International journal of molecular sciences · 2026Review
- Keratin 5 marks cancer-propagating cells sustained by an osteopontin-producing niche in high-grade serous ovarian carcinoma.Cancer heterogeneity and plasticity · 2026Article
- Coconut oil/lauric acid-based nanodrug formulation: a multifunctional platform for enhancing cancer therapy and mitigating toxicity.Frontiers in cell and developmental biology · 2026Review
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- [Role of hyaluronic acid synthases in female infertility-related diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Fumiquinazolines F and G from the FungusInternational journal of molecular sciences · 2025Article
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Sensitisation of HeLa Cell Cultures to Xanthone Treatment by RNAi-Mediated Silencing of NANOG and STAT3.Current issues in molecular biology · 2025Article
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- CD44 Variant Expression in Follicular Cell-Derived Thyroid Cancers: Implications for Overcoming Multidrug Resistance.Molecules (Basel, Switzerland) · 2025Review
- Genes and proteins expression profile of 2D vs 3D cancer models: a comparative analysis for better tumor insights.Cytotechnology · 2025Review
- Advances in S100 protein family for gynecological malignancies.Discover oncology · 2025Review
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Drug-tolerant persister cells in acute myeloid leukemia: pressing challenge and promising new strategies for treatment.Frontiers in medicine · 2025Review
194 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hyaluronan (HA) is a major glycosaminoglycan in the extracellular matrix whose expression is tightly linked to multidrug resistance and tumor progression. In this study we investigated HA-induced interaction between CD44 (a HA receptor) and Nanog (an embryonic stem cell transcription factor) in both human breast tumor cells (MCF-7 cells) and human ovarian tumor cells (SK-OV-3.ipl cells). Using a specific primer pair to amplify Nanog by reverse transcriptase-PCR, we detected the expression of Nanog transcript in both tumor cell lines. In addition, our results reveal that HA binding to these tumor cells promotes Nanog protein association with CD44 followed by Nanog activation and the expression of pluripotent stem cell regulators (e.g. Rex1 and Sox2). Nanog also forms a complex with the "signal transducer and activator of transcription protein 3" (Stat-3) in the nucleus leading to Stat-3-specific transcriptional activation and multidrug transporter, MDR1 (P-glycoprotein) gene expression. Furthermore, we observed that HA-CD44 interaction induces ankyrin (a cytoskeletal protein) binding to MDR1 resulting in the efflux of chemotherapeutic drugs (e.g. doxorubicin and paclitaxel (Taxol)) and chemoresistance in these tumor cells. Overexpression of Nanog by transfecting tumor cells with Nanog cDNA stimulates Stat-3 transcriptional activation, MDR1 overexpression, and multidrug resistance. Down regulation of Nanog signaling or ankyrin function (by transfecting tumor cells with Nanog small interfering RNA or ankyrin repeat domain cDNA) not only blocks HA/CD44-mediated tumor cell behaviors but also enhances chemosensitivity. Taken together, these findings suggest that targeting HA/CD44-mediated Nanog-Stat-3 signaling pathways and ankyrin/cytoskeleton function may represent a novel approach to overcome chemotherapy resistance in some breast and ovarian tumor cells displaying stem cell marker properties during tumor progression.
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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.