ArticleHepatology (Baltimore, Md.)2021
Overexpression of Mothers Against Decapentaplegic Homolog 7 Activates the Yes-Associated Protein/NOTCH Cascade and Promotes Liver Carcinogenesis in Mice and Humans.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Targeting the Hippo pathway in pulmonary arterial hypertension: emerging pharmacological strategies.Journal of hypertension · 2026Review
- Uncoupling Metastasis and Epithelial-to-Mesenchymal Transition in sgP19/kRAS-Driven Spontaneous Metastatic Liver Tumor Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025Review
- CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling.Cell death & disease · 2025Article
- Review
- NCardiovascular diabetology · 2024Article
- Aspirin attenuates the detrimental effects of TNF-α on BMMSC stemness by modulating the YAP-SMAD7 axis.Molecular medicine (Cambridge, Mass.) · 2024Article
- STAT3 palmitoylation initiates a positive feedback loop that promotes the malignancy of hepatocellular carcinoma cells in mice.Science signaling · 2023Article
- Review
- Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Review
- Suspension state and shear stress enhance breast tumor cells EMT through YAP by microRNA-29b.Cell biology and toxicology · 2023Article
- Yes-Associated Protein and Transcriptional Coactivator with PDZ-Binding Motif in Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- Role of Yes-Associated Protein in Psoriasis and Skin Tumor Pathogenesis.Journal of personalized medicine · 2022Review
- Review
- YAP Activates STAT3 Signalling to Promote Colonic Epithelial Cell Proliferation in DSS-Induced Colitis and Colitis Associated Cancer.Journal of inflammation research · 2022Article
- Phosphatidylinositol glycan anchor biosynthesis, class C is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Article
- Article
- DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer.Cells · 2021Article
- Effect of ISM1 on the Immune Microenvironment and Epithelial-Mesenchymal Transition in Colorectal Cancer.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
BACKGROUND AND
aimsMothers against decapentaplegic homolog (SMAD) 7 is an antagonist of TGF-β signaling. In the present investigation, we sought to determine the relevance of SMAD7 in liver carcinogenesis using in vitro and in vivo approaches. APPROACH AND
resultsWe found that SMAD7 is up-regulated in a subset of human HCC samples with poor prognosis. Gene set enrichment analysis revealed that SMAD7 expression correlates with activated yes-associated protein (YAP)/NOTCH pathway and cholangiocellular signature genes in HCCs. These findings were substantiated in human HCC cell lines. In vivo, overexpression of Smad7 alone was unable to initiate HCC development, but it significantly accelerated c-Myc/myeloid cell leukemia 1 (MCL1)-induced mouse HCC formation. Consistent with human HCC data, c-Myc/MCL1/Smad7 liver tumors exhibited an increased cholangiocellular gene expression along with Yap/Notch activation and epithelial-mesenchymal transition (EMT). Intriguingly, blocking of the Notch signaling did not affect c-Myc/MCL1/Smad7-induced hepatocarcinogenesis while preventing cholangiocellular signature expression and EMT, whereas ablation of Yap abolished c-Myc/MCL1/Smad7-driven HCC formation. In mice overexpressing a myristoylated/activated form of AKT, coexpression of SMAD7 accelerated carcinogenesis and switched the phenotype from HCC to intrahepatic cholangiocarcinoma (iCCA) lesions. In human iCCA, SMAD7 expression was robustly up-regulated, especially in the most aggressive tumors, and directly correlated with the levels of YAP/NOTCH targets as well as cholangiocellular and EMT markers.
conclusionsThe present data indicate that SMAD7 contributes to liver carcinogenesis by activating the YAP/NOTCH signaling cascade and inducing a cholangiocellular and EMT signature.
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