ArticleCell communication and signaling : CCS2018
Inhibition of CREB binding protein-beta-catenin signaling down regulates CD133 expression and activates PP2A-PTEN signaling in tumor initiating liver cancer cells.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Beyond a cancer stem cell marker: molecular state dependent functions of CD133 and state targeted therapy.Biomarker research · 2026Review
- Article
- Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease.Cellular & molecular biology letters · 2024Review
- Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment.Stem cell reviews and reports · 2024Review
- Genetic heterogeneity of liver cancer stem cells.Anatomy & cell biology · 2023Article
- Microvesicles: the functional mediators in sorafenib resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Epigenetically modulated miR-1224 suppresses the proliferation of HCC through CREB-mediated activation of YAP signaling pathway.Molecular therapy. Nucleic acids · 2021Article
- The Effect of Metformin on the Proliferation, Apoptosis and CD133 mRNA Expression of Colon Cancer Stem Cells by Upregulation of miR 342-3p.Drug design, development and therapy · 2021Article
- Wnt3a/β-Catenin/CBP Activation in the Progression of Cervical Intraepithelial Neoplasia.Pathology oncology research : POR · 2021Article
- High-throughput profiling of diapause regulated genes from Trichogramma dendrolimi (Hymenoptera: Trichogrammatidae).BMC genomics · 2020Article
- Recent advances in PTEN signalling axes in cancer.Faculty reviews · 2020Review
- The Emerging Roles of Cancer Stem Cells and Wnt/Beta-Catenin Signaling in Hepatoblastoma.Cancers · 2019Review
- Correlation of p16 and cyclin D1 expression with the incidence and prognosis of cardiac carcinoma.Oncology letters · 2019Article
- CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2.Oncogene · 2019Article
- Inhibition of CD133 Overcomes Cisplatin Resistance Through Inhibiting PI3K/AKT/mTOR Signaling Pathway and Autophagy in CD133-Positive Gastric Cancer Cells.Technology in cancer research & treatment · 2019Article
- CD133 as a regulator of cancer metastasis through the cancer stem cells.The international journal of biochemistry & cell biology · 2019Review
- Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies.Therapeutic advances in medical oncology · 2018Review
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe WNT-beta-catenin pathway is known to regulate cellular homeostasis during development and tissue regeneration. Activation of WNT signaling increases the stability of cytoplasmic beta-catenin and enhances its nuclear translocation. Nuclear beta-catenin function is regulated by transcriptional co-factors such as CREB binding protein (CBP) and p300. Hyper-activated WNT-beta-catenin signaling is associated with many cancers. However, its role in inducing stemness to liver cancer cells, its autoregulation and how it regulates tumor suppressor pathways are not well understood. Here we have investigated the role of CBP-beta-catenin signaling on the expression of CD133, a known stem cell antigen and PP2A-PTEN pathway in tumor initiating liver cancer cells.
methodsHuman hepatoblastoma cell line HepG2 and clonally expanded CD133 expressing tumor initiating liver cells (TICs) from premalignant murine liver were used in this study. CBP-beta-catenin inhibitor ICG001 was used to target CBP-beta catenin signaling in liver cancer cells in vitro. Western blotting and real time PCR (qPCR) were used to quantify protein expression/phosphorylation and mRNA levels, respectively. CBP and CD133 gene silencing was performed by siRNA transfection. Fluorescence Activated Cell Sorting (FACS) was performed to quantify CD133 positive cells. Protein Phosphatase (PP2A) activity was measured after PP2AC immunoprecipitation.
resultsCBP inhibitor ICG001 and CBP silencing significantly reduced CD133 expression and anchorage independent growth in HepG2 and murine TICs. CD133 silencing in TICs decreased cell proliferation and expression levels of cell cycle regulatory genes, CyclinD1 and CyclinA2. ICG001 treatment and CBP silencing reduced the levels of phospho
conclusionsCBP-beta-catenin signaling promotes stemness via CD133 induction and cell proliferation in TICs. We found a novel functional link between CBP-beta-catenin and PP2A-PTEN-AKT pathway in liver TICs. Therefore, CBP-beta-catenin-PP2A-PTEN-AKT signaling axis could be a novel therapeutic target to prevent liver tumor initiation and cancer recurrence.
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