ArticleCancer medicine2019
CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Beyond a cancer stem cell marker: molecular state dependent functions of CD133 and state targeted therapy.Biomarker research · 2026Review
- From matrix to nucleus: CD44 as a central regulator of inflammaging, autophagy, and tissue homeostasis.Biogerontology · 2026Review
- Innovative strategies to overcome cancer drug resistance: from nanodelivery systems to targeted therapeutics.Discover oncology · 2026Review
- Review
- Epithelial-Mesenchymal Transition and Stress Adaptations Underlie Yttrium-90 Resistance in Liver Cancer Cell Lines.Cancer research communications · 2026Article
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- Article
- HBx Drives Liver Cancer Stem Cell Generation Through Stimulating Glucose Metabolic Reprogramming.Journal of cellular and molecular medicine · 2025Article
- Sorafenib-Drug Delivery Strategies in Primary Liver Cancer.Journal of functional biomaterials · 2025Review
- Evaluation of hepatic cancer stem cells (CDMolecular biology reports · 2025Article
- Farnesoid X Receptor Attenuates the Tumorigenicity of Liver Cancer Stem Cells by Inhibiting STAT3 Phosphorylation.International journal of molecular sciences · 2025Article
- Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.Frontiers in cell and developmental biology · 2025Review
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Targeting Hepatic Cancer Stem Cells (CSCs) and Related Drug Resistance by Small Interfering RNA (siRNA).Cell biochemistry and biophysics · 2024Review
- Clinical and prognostic significance of CD27 and CD44 expression patterns in Egyptian pediatric patients with B-precursor acute lymphoblastic leukemia.Hematology, transfusion and cell therapy · 2024Article
- Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.International journal of stem cells · 2024Review
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- Systems biology approach to identify biomarkers and therapeutic targets for colorectal cancer.Biochemistry and biophysics reports · 2024Article
- Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma.Heliyon · 2024Review
- Emodin is a Potential Drug Targeting CD44-positive Hepatocellular Cancer.Current cancer drug targets · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for cancer because they play important roles in the development and aggravation of cancer. CD44 is expressed as a standard isoform (CD44s) and several variant isoforms. CD44v is a major isoform expressed on CSCs of a variety of tumors and has been extensively studied. However, HCC tissues dominantly express CD44s, whose function in CSCs remains unclear. In the present study, we investigated the roles of CD44s in CSCs of HCC. Knock-out of the CD44 gene in HuH7 HCC cells on which only CD44s is expressed resulted in decreased spheroid formation and increased drug sensitivity. The expression of CSC marker genes, including CD133 and EpCAM, was significantly downregulated in the spheroids of CD44-deficient cells compared with those in the spheroids of HuH7 cells. In addition, CD44 deficiency impaired antioxidant capacity, concomitant with downregulation of glutathione peroxidase 1 (GPX1) and thioredoxin. Because GPX1 uses the reduced form of glutathione (GSH) to regenerate oxidized cellular components, GSH levels were significantly increased in the CD44-deficient cells. We also found that NOTCH3 and its target genes were downregulated in the spheroids of CD44-deficient cells. NOTCH3 expression in HCC tissues was significantly increased compared with that in adjacent nontumor liver tissues and was correlated with CD44 expression. These results suggest that CD44s is involved in maintenance of CSCs in a HCC cell line, possibly through the NOTCH3 signaling pathway.
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