ArticleCell death & disease2018
Crosstalk between hepatic tumor cells and macrophages via Wnt/β-catenin signaling promotes M2-like macrophage polarization and reinforces tumor malignant behaviors.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.
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Who cites it
210 citing papers in PubMed, 306 citations in OpenAlex.
- Unmasking Wnt-driven HCC: Inhibiting SMYD2 to overcome immune resistance.Molecular therapy. Oncology · 2026Article
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Targeting SMYD2 improves immunotherapy response in experimental hepatocellular carcinoma.Molecular therapy. Oncology · 2026Article
- PRSS23 functions downstream of ZEB1 to promote esophageal squamous cell carcinoma progression by driving M2 polarization of tumor associated macrophages.Molecular and cellular biochemistry · 2026Article
- MATR3 regulates METTL3-Mediated mJournal of bioenergetics and biomembranes · 2026Article
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- PRC1 promotes immunosuppressive macrophages in sepsis via β-catenin/STAT3 signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Total Saponins from Rhizoma Panacis Majoris Promote Wound Healing in Diabetic Rats by Regulating Inflammatory Dysregulation.International journal of molecular sciences · 2026Article
- Whole-genome resequencing reveals genomic characteristics and candidate genomic regions potentially associated with local adaptation of Leiwuqi yak (Frontiers in veterinary science · 2026Article
- Article
- Prolonged Wnt3a exposure tolerizes macrophages to inflammatory stimuli.Frontiers in immunology · 2026Article
- Vitamin DScientific reports · 2025Article
- Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.Cancer cell international · 2025Review
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Growth differentiation factor 11 modulates metabolism, mitigating the pro-tumoral behavior provided by M2-like macrophages in hepatocellular carcinoma-derived cells.World journal of gastroenterology · 2025Article
- Article
- Cedrol impedes lung cancer metastasis by reducing tumor-associated macrophage polarization mediated by MYC-driven aerobic glycolysis.Human cell · 2025Article
- Delivered baicalein immunomodulatory hydrogel with dual properties of pH-responsive and anti-infection orchestrates pro-regenerative response of macrophages for enhanced hypertrophic scars therapy.Materials today. Bio · 2025Article
- mOncogene · 2025Article
150 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) are a major component of tumor microenvironment (TME) and play pivotal roles in the progression of hepatocellular carcinoma (HCC). Wnt signaling is evolutionarily conserved and participates in liver tumorigenesis. Several studies have shown that macrophage-derived Wnt ligands can activate Wnt signaling in tumor cells. However, whether Wnt ligands secreted by tumor cells can trigger Wnt signaling in macrophages is still elusive. In this study, we first verified that canonical Wnt/β-catenin signaling was activated during monocyte-to-macrophage differentiation and in M2-polarized macrophages. Knockdown of β-catenin in M2 macrophages exhibited stronger antitumor characteristics when cocultured with Hepa1-6 HCC cells in a series of experiments. Activation of Wnt signaling promoted M2 macrophage polarization through c-Myc. Moreover, co-culturing naïve macrophages with Hepa1-6 HCC cells in which Wnt ligands secretion was blocked by knockdown of Wntless inhibited M2 polarization in vitro. Consistently, the growth of HCC tumor orthotopically inoculated with Wntless-silenced Hepa1-6 cells was impeded, and the phenotype of M2-like TAMs was abrogated due to attenuated Wnt/β-catenin signaling in TAMs, leading to subverted immunosuppressive TME. Finally, we confirmed the correlation between M2 macrophage polarization and nuclear β-catenin accumulation in CD68
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