ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Imbalance of TGF-β1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58 citing papers in PubMed, 88 citations in OpenAlex.
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- ID1 in TAMs promoted the progression of non-small-cell carcinoma via increasing NF-κB/NPM1/SHP1/SHP2 signaling induced M2 polarization.Scientific reports · 2026Article
- LINE-1 retrotransposition modulates metabolic stress and promotes cuproptosis resistance in lung squamous cell carcinoma by disrupting mitochondrial membrane homeostasis.Journal of translational medicine · 2026Article
- Molecular mechanisms of tumor-associated macrophages in hepatocellular carcinoma development and therapy.World journal of gastroenterology · 2026Review
- LZTR1 Loss Reduces Vimentin Expression and Motility in Hep3B Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2026Article
- Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- 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
- Macrophage-centered therapy strategies: A promising weapon in cancer immunotherapy.Asian journal of pharmaceutical sciences · 2025Review
- The Pleiotropic Role of the MicroRNA-17-92 Cluster in Cardiovascular Diseases and Cancer.Reviews in cardiovascular medicine · 2025Review
- A Comprehensive Review Exploring the Role of Bone Morphogenetic Proteins [BMP]: Biological Mechanisms.Current issues in molecular biology · 2025Review
- Using β-Elemene to reduce stemness and drug resistance in osteosarcoma: A focus on the AKT/FOXO1 signaling pathway and immune modulation.Journal of bone oncology · 2025Article
- The microenvironment cell index is a novel indicator for the prognosis and therapeutic regimen selection of cancers.Journal of translational medicine · 2025Article
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- Prospect of extracellular vesicles in tumor immunotherapy.Frontiers in immunology · 2025Review
- Crosstalk Between Extracellular Vesicles and Regulatory T Cells Across Cancers: From Interaction to Therapeutic Potential.International journal of nanomedicine · 2025Review
- Roles of transforming growth factor-β signaling in liver disease.World journal of hepatology · 2024Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
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Abstract
The transforming growth factor-beta (TGF-β) signaling pathway is the predominant cytokine signaling pathway in the development and progression of hepatocellular carcinoma (HCC). Bone morphogenetic protein (BMP), another member of the TGF-β superfamily, has been frequently found to participate in crosstalk with the TGF-β pathway. However, the complex interaction between the TGF-β and BMP pathways has not been fully elucidated in HCC. We found that the imbalance of TGF-β1/BMP-7 pathways was associated with aggressive pathological features and poor clinical outcomes in HCC. The induction of the imbalance of TGF-β1/BMP-7 pathways in HCC cells could significantly promote HCC cell invasion and stemness by increasing inhibitor of differentiation 1 (ID1) expression. We also found that the microRNA (miR)-17-92 cluster, originating from the extracellular vesicles (EVs) of M2-polarized tumor-associated macrophages (M2-TAMs), stimulated the imbalance of TGF-β1/BMP-7 pathways in HCC cells by inducing TGF-β type II receptor (TGFBR2) post-transcriptional silencing and inhibiting activin A receptor type 1 (ACVR1) post-translational ubiquitylation by targeting Smad ubiquitylation regulatory factor 1 (Smurf1). In vivo, short hairpin (sh)-MIR17HG and ACVR1 inhibitors profoundly attenuated HCC cell growth and metastasis by rectifying the imbalance of TGF-β1/BMP-7 pathways. Therefore, we proposed that the imbalance of TGF-β1/BMP-7 pathways is a feasible prognostic biomarker and recovering the imbalance of TGF-β1/BMP-7 pathways might be a potential therapeutic strategy for HCC.
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