ArticleCancer science2016
CD44 variant-dependent redox status regulation in liver fluke-associated cholangiocarcinoma: A target for cholangiocarcinoma treatment.
Article in Cancer science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- From matrix to nucleus: CD44 as a central regulator of inflammaging, autophagy, and tissue homeostasis.Biogerontology · 2026Review
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- CD44v9 Expression in Pretreatment Biopsies as a Predictor of Chemotherapy Resistance in Gastric Cancer.Cancers · 2025Article
- CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb.FEBS open bio · 2025Article
- Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.The American journal of pathology · 2025Review
- Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma.Antioxidants (Basel, Switzerland) · 2023Review
- Targeting CD44 Variant 5 with an Antibody-Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.Cancer research · 2023Article
- NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1.International journal of biological sciences · 2023Article
- Article
- miR-28-5p inhibits cholangiocarcinoma progression and predicts good prognosis of patients.Cell cycle (Georgetown, Tex.) · 2022Article
- Article
- Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis.Oncology letters · 2022Review
- Review
- CD44: A Multifunctional Mediator of Cancer Progression.Biomolecules · 2021Review
- Oncogenic transformation of NIH/3T3 cells by the overexpression of L-type amino acid transporter 1, a promising anti-cancer target.Oncotarget · 2021Article
- Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment.Biomolecules · 2021Article
- Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models.Cancer & metabolism · 2021Article
- Cancer Stem Cells in Intrahepatic Cholangiocarcinoma; Their Molecular Basis, and Therapeutic Implications.Frontiers in physiology · 2021Review
- CD44 modulates metabolic pathways and altered ROS-mediated Akt signal promoting cholangiocarcinoma progression.PloS one · 2021Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of CD44, especially the variant isoforms (CD44v) of this major cancer stem cell marker, contributes to reactive oxygen species (ROS) defense through stabilizing xCT (a cystine-glutamate transporter) and promoting glutathione synthesis. This enhances cancer development and increases chemotherapy resistance. We investigate the role of CD44v in the regulation of the ROS defense system in cholangiocarcinoma (CCA). Immunohistochemical staining of CD44v and p38(MAPK) (a major ROS target) expression in Opisthorchis viverrini-induced hamster CCA tissues (at 60, 90, 120, and 180 days) reveals a decreased phospho-p38(MAPK) signal, whereas the CD44v signal was increased during bile duct transformation. Patients with CCA showed CD44v overexpression and negative-phospho-p38(MAPK) patients a significantly shorter survival rate than the low CD44v signal and positive-phospho-p38(MAPK) patients (P = 0.030). Knockdown of CD44 showed that xCT and glutathione levels were decreased, leading to a high level of ROS. We examined xCT-targeted CD44v cancer stem cell therapy using sulfasalazine. Glutathione decreased and ROS increased after the treatment, leading to inhibition of cell proliferation and induction of cell death. Thus, the accumulation of CD44v leads to the suppression of p38(MAPK) in transforming bile duct cells. The redox status regulation of CCA cells depends on the expression of CD44v to contribute the xCT function and is a link to the poor prognosis of patients. Thus, an xCT inhibitor could inhibit cell growth and activate cell death. This suggests that an xCT-targeting drug may improve CCA therapy by sensitization to the available drug (e.g. gemcitabine) by blocking the mechanism of the cell's ROS defensive system.
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