ArticleCancer biology & therapy2016
Overexpression of hepatocyte nuclear factor 4α in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/β-catenin signaling pathway downregulation.
Article in Cancer biology & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review.Stem cell research & therapy · 2018Pooled it
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- Delineating the role of nuclear receptors in colorectal cancer, a focused review.Discover oncology · 2024Review
- Advances and clinical challenges of mesenchymal stem cell therapy.Frontiers in immunology · 2024Review
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Intestinal Wnt in the transition from physiology to oncology.World journal of clinical oncology · 2022Review
- The Roles of Mesenchymal Stem Cells in Gastrointestinal Cancers.Frontiers in immunology · 2022Review
- Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.Stem cells international · 2022Article
- Review
- Importance of the origin of mesenchymal (stem) stromal cells in cancer biology: "alliance" or "war" in intercellular signals.Cell & bioscience · 2021Review
- Controversial roles of hepatocyte nuclear receptor 4 α on tumorigenesis.Oncology letters · 2021Review
- Mesenchymal stem cells as professional actors in gastrointestinal cancer therapy: From Naïve to genetically modified.Iranian journal of basic medical sciences · 2021Review
- Functional inhibition of Oct leads to HNF4α upregulation.Experimental and therapeutic medicine · 2021Article
- Genetic modification by overexpression of target gene in mesenchymal stromal cell for treating liver diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment.Experimental & molecular medicine · 2021Review
- Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine.Stem cells international · 2021Review
- [Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Review
- Efficacy of mesenchymal stem cells in the treatment of gastrointestinal malignancies.World journal of gastrointestinal oncology · 2020Review
- Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.Frontiers in cell and developmental biology · 2020Review
- Sorafenib and Mesenchymal Stem Cell Therapy: A Promising Approach for Treatment of HCC.Evidence-based complementary and alternative medicine : eCAM · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) hold promise as cellular vehicles for the delivery of therapeutic gene products because they can be isolated, expanded, and genetically modified in vitro and possess tumor-oriented homing capacity in vivo. (1) Hepatocyte nuclear factor 4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis (HCC). (2,3) We have previously demonstrated that overexpression of HNF4α activates various hepatic-specific genes and enhances MSC differentiation. (4) However, the extent that overexpression of HNF4α in MSCs influences HCC progression has yet to be examined. Here we sought to investigate what effect MSCs overexpressing HNF4α (MSC-HNF4α) have on human hepatoma cells in vitro and in vivo. Conditioned medium collected from in vitro MSC-HNF4α cultures significantly inhibited hepatoma cell growth and metastasis compared with controls. Additionally, nude mice administered MSC-HNF4α exhibited significantly smaller tumors compared with controls in vivo. Immunoblot analysis of HCC cells treated with MSC-HNF4α displayed downregulated β-catenin, cyclinD1, c-Myc, MMP2 and MMP9. Taken together, our results demonstrate that MSC-HNF4α inhibits HCC progression by reducing hepatoma cell growth and metastasis through downregulation of the Wnt/β-catenin signaling pathway.
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Registered trials
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