ArticleHepatology international2020
Wnt status-dependent oncogenic role of BCL9 and BCL9L in hepatocellular carcinoma.
Article in Hepatology international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting BCL9/BCL9L enhances CD4Acta pharmacologica Sinica · 2026Article
- BCL9 as a Key Player in Wnt/β-catenin Signaling: Implications for Osteogenesis, Tissue Repair, and Oncology.Applied biochemistry and biotechnology · 2026Review
- Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell (cDC1) activation and tumor infiltration.Signal transduction and targeted therapy · 2024Article
- Body Weight Correlates with Molecular Variances in Patients with Cancer.Cancer research · 2024Article
- The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities.Genes & diseases · 2024Review
- Polychlorinated biphenyls alter hepatic m6A mRNA methylation in a mouse model of environmental liver disease.Environmental research · 2023Article
- Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma.Pharmaceutics · 2022Review
- Article
- MiR-129-5p exerts Wnt signaling-dependent tumor-suppressive functions in hepatocellular carcinoma by directly targeting hepatoma-derived growth factor HDGF.Cancer cell international · 2022Article
- Wnt/β-Catenin Signalling and Its Cofactor BCL9L Have an Oncogenic Effect in Bladder Cancer Cells.International journal of molecular sciences · 2022Article
- ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer.Nature communications · 2022Article
- The role of BCL9 genetic variation as a biomarker for hepatitis C-related hepatocellular carcinoma in Egyptian patients.Journal, genetic engineering & biotechnology · 2022Article
- Development of Molecular Mechanisms and Their Application on Oncolytic Newcastle Disease Virus in Cancer Therapy.Frontiers in molecular biosciences · 2022Review
- Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma.Acta histochemica et cytochemica · 2021Article
- Discovery of an Orally Bioavailable Small-Molecule Inhibitor for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction.Journal of medicinal chemistry · 2021Article
- Matrix stiffness promotes glioma cell stemness by activating BCL9L/Wnt/β-catenin signaling.Aging · 2021Article
- Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis.Cell death & disease · 2021Article
- Cell Fusion-Related Proteins and Signaling Pathways, and Their Roles in the Development and Progression of Cancer.Frontiers in cell and developmental biology · 2021Review
- Deficiency of Mettl3 in Bladder Cancer Stem Cells Inhibits Bladder Cancer Progression and Angiogenesis.Frontiers in cell and developmental biology · 2021Article
- Targeting Oncogenic WNT Signalling with WNT Signalling-Derived Peptides.Handbook of experimental pharmacology · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundActivation of Wnt/β-catenin pathway is a frequent event in hepatocellular carcinoma and is associated with enhanced cell survival and proliferation. Therefore, targeting this signaling pathway is discussed as an attractive therapeutic approach for HCC treatment. BCL9 and BCL9L, two homologous coactivators of the β-catenin transcription factor complex, have not yet been comprehensively characterized in HCC. We aimed to elucidate the roles of BCL9 and BCL9L, especially regarding Wnt/β-catenin signaling and their prognostic value in HCC.
methodsExpression of BCL9/BCL9L was determined in HCC cell lines (HLE, HLF, Huh7, HepG2, Hep3B, and Huh6) and normal liver cell lines (THLE-2 and THLE-3). To analyze proliferation and apoptosis, BCL9 and/or BCL9L were knocked down in Wnt-inactive HLE and Wnt-active HepG2 and Huh6 cells using siRNA. Subsequently, Wnt reporter assays were performed in HepG2 and Huh6 cells. BCL9 and BCL9L expression, clinicopathological and survival data of public HCC datasets were analyzed, taking the Wnt signaling status into account.
resultsKnockdown of BCL9L, but not of BCL9, reduced Wnt signaling activity. Knockdown of BCL9 and/or BCL9L reduced cell viability and increased apoptosis of Wnt-inactive HCC cells, but had no effect in Wnt-active cells. Expression of BCL9 and BCL9L was upregulated in human HCC and increased with progressing dedifferentiation. For BCL9L, higher expression was observed in tumors of larger size. Overexpression of BCL9 and BCL9L correlated with poor overall survival, especially in HCC without activated Wnt signaling.
conclusionOncogenic BCL9 proteins represent promising targets for cancer therapy and inhibiting them may be particularly beneficial in Wnt-inactive HCCs.
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