ArticleOncotarget2018
Differentiation-inducing therapeutic effect of Notch inhibition in reversing malignant transformation of liver normal stem cells via MET.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Evaluation of different media compositions promoting hepatocyte differentiation in the canine liver organoid model.Heliyon · 2024Article
- Integrating single cell analysis and machine learning methods reveals stem cell-related gene S100A10 as an important target for prediction of liver cancer diagnosis and immunotherapy.Frontiers in immunology · 2024Article
- Drug Repurposing by Tumor Tissue Editing.Frontiers in oncology · 2022Review
- Hepatic Cancer Stem Cells: Molecular Mechanisms, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2021Review
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- Review
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Long non‑coding RNA HOTAIR promotes burn wound healing by regulating epidermal stem cells.Molecular medicine reports · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes.
resultsInhibition of Notch signaling pathway can down-regulate the stemness-related cancer markers, lower the proliferative status, alleviate the invasive characteristic, or attenuate the metastasis tendency. What is more, it can help the malignantly transformed cells to regain the mature hepatic function of glucagon synthesis, urea metabolism, albumin production, and indocyanine-green (ICG) clearance. MATERIALS AND
methodsHOX transcript antisense RNA (HOTAIR) expression was enhanced in LNSCs via lentivirus transduction to set up the malignant transformation cellular model. Then, a Notch inhibitor was applied to induce malignantly transformed cells differentiate into mature hepatocytes, and malignant abilities of proliferation, invasiveness, tumorigenesis as well as mature hepatocyte function were observed and compared.
conclusionsThe data demonstrate that the anti-tumor effects of Notch inhibition may lie not only on killing the cancer cells or LCSCs directly, it can also induce the LCSCs differentiation into mature hepatocytes via mesenchymal-epithelial transition (MET) progress or downgrade the malignancy.
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