ArticleScientific reports2016
Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- METTL14-mediated m6A modification of CXCL9 mRNA regulates macrophage CS polarization to suppress OSCC growth and stemness.Functional & integrative genomics · 2026Article
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- CENP-F promotes HCC cell proliferation mediated by super enhancer reader BRD4.Discover oncology · 2025Article
- Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- Novel biomarkers for monitoring and management of hepatocellular carcinoma.Cancer cell international · 2024Review
- High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling.Biomolecules · 2024Article
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- Tramadol suppresses growth of orthotopic liver tumors via promoting M1 macrophage polarization in the tumor microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Activation of CTU2 expression by LXR promotes the development of hepatocellular carcinoma.Cell biology and toxicology · 2024Article
- LncRNA ANRIL Promotes Glucose Metabolism and Proliferation of Colon Cancer in a High-Glucose Environment and is Associated with Worse Outcome in Diabetic Colon Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- LncRNA RASAL2-AS1 promotes METTL14-mediated m6A methylation in the proliferation and progression of head and neck squamous cell carcinoma.Cancer cell international · 2024Article
- Ubiquitin B, Ubiquitin C, and β-Catenin as Promising Diagnostic and Prognostic Tools in Prostate Cancer.Cancers · 2024Article
- TEP SNORD12B, SNORA63, and SNORD14E as novel biomarkers for hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC).Cancer cell international · 2024Article
- Article
- Tumor cell malignancy: A complex trait built through reciprocal interactions between tumors and tissue-body system.iScience · 2022Review
- Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- The angiotensin-converting enzyme inhibitor, captopril, suppressed hepatic stellate cell activation via NF-kappaB or wnt3α/β-catenin pathway.Bioengineered · 2021Article
- A literature review on function and regulation mechanism of DKK4.Journal of cellular and molecular medicine · 2021Review
- c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6 Transcriptional Activation.Frontiers in endocrinology · 2021Article
- The Role of Aberrant Metabolism in Cancer: Insights Into the Interplay Between Cell Metabolic Reprogramming, Metabolic Syndrome, and Cancer.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elevated glycemic index, an important feature of diabetes is implicated in an increased risk of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of this association are relatively less explored. Present study investigates the effect of hyperglycemia over HCC proliferation. We observed that high glucose culture condition (HG) specifically activates canonical Wnt signaling in HCC cells, which is mediated by suppression of DKK4 (a Wnt antagonist) expression and enhanced β-catenin level. Functional assays demonstrated that a normoglycemic culture condition (NG) maintains constitutive expression of DKK4, which controls HCC proliferation rate by suppressing canonical Wnt signaling pathway. HG diminishes DKK4 expression leading to loss of check at G0/G1/S phases of the cell cycle thereby enhancing HCC proliferation, in a β-catenin dependent manner. Interestingly, in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of β-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose facilitated HCC proliferation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.