ArticleBMC cancer2018
Enrichment of cancer stem cells via β-catenin contributing to the tumorigenesis of hepatocellular carcinoma.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
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- Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways.International journal of molecular sciences · 2025Article
- Dujieqing decoction suppresses multiple myeloma growth by inhibiting the Wnt/β-catenin pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Targeting YTHDF2 with pH-responsive siRNA nanoparticles suppresses MYC m6A modification and restores antitumor immunity in hepatocellular carcinoma.Journal of nanobiotechnology · 2025Article
- Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches.Cancers · 2025Review
- Wnt Signaling in Hepatocellular Carcinoma: Biological Mechanisms and Therapeutic Opportunities.Cells · 2024Review
- Understanding the autophagic functions in cancer stem cell maintenance and therapy resistance.Expert reviews in molecular medicine · 2024Review
- WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities.Genes & diseases · 2024Review
- Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma.World journal of gastroenterology · 2024Article
- Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.Frontiers in oncology · 2024Review
- From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment.Journal of medicinal chemistry · 2023Review
- Anticancer Potential of Apigenin and Isovitexin with Focus on Oncogenic Metabolism in Cancer Stem Cells.Metabolites · 2023Review
- Cellular and Molecular Biology of Cancer Stem Cells of Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Targeting Wnt-β-Catenin Signaling Pathway for Hepatocellular Carcinoma Nanomedicine.Gastro hep advances · 2023Review
- Overexpression ofMolecules and cells · 2022Article
- The Molecular and Cellular Strategies of Glioblastoma and Non-Small-Cell Lung Cancer Cells Conferring Radioresistance.International journal of molecular sciences · 2022Review
- Article
- Perindopril sensitizes hepatocellular carcinoma to chemotherapy: A possible role of leptin / Wnt/ β-catenin axis with subsequent inhibition of liver cancer stem cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Review
- Doxorubicin-induced senescence promotes stemness and tumorigenicity in EpCAM-/CD133- nonstem cell population in hepatocellular carcinoma cell line, HuH-7.Molecular oncology · 2021Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is among the deadliest cancers due to its heterogeneity, contributing to chemoresistance and recurrence. Cancer stem-like cells (CSCs) are suggested to play an important role in HCC tumorigenesis. This study investigates the role of Wnt/β-catenin pathway in CSC enrichment and the capabilities of these CSCs in tumor initiation in orthotopic immunocompetent mouse model.
methodsHCC-CSCs were enriched using established serum-free culture method. Wnt/β-catenin pathway activation and its components were analyzed by western blot and qRT-PCR. The role of β-catenin in enrichment of CSC spheroids was confirmed using siRNA interference. Tumorigenic capabilities were confirmed using orthotopic immunocompetent mouse model by injecting 2 × 10
resultsThe serum-free cultured Hepa1-6 cells demonstrated self-renewal, spheroid formation, higher EpCAM expression, increased Hoechst-33342 efflux, and upregulated Wnt/β-catenin signaling. Wnt/β-catenin pathway upregulation was implicated with the downstream targets, i.e., c-MYC, Cyclin-D1, and LEF1. Also, we found that GSK-3β serine-9 phosphorylation increased in Hepa1-6 spheroids. Silencing β-catenin by siRNA reversed spheroid formation phenotype. Mice injected with Hepa1-6 CSC spheroids showed aggressive tumor initiation and growth compared with mice injected with control cells.
conclusionsSuccessfully induced Hepa1-6 spheroids were identified with CSC-like properties. Aberrant β-catenin upregulation mediated by GSK-3β was observed in the Hepa1-6 spheroids. The β-catenin mediated CSC enrichment in the induced spheroids possesses the capability of tumor initiation in immunocompetent mice. Our study suggests plausible cell dedifferentiation mediated by β-catenin contributes to CSC-initiated HCC tumor growth in vivo.
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