ArticleOncogenesis2017
Hepatocyte-specific Smad7 deletion accelerates DEN-induced HCC via activation of STAT3 signaling in mice.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- In vitro properties of patient serum predict clinical outcome after high dose rate brachytherapy of hepatocellular carcinoma.Molecular oncology · 2026Article
- TGFβ pathway represses hepatic ribosome biogenesis and protein synthesis by regulating p70S6K-S6RP proteins.Cellular & molecular biology letters · 2026Article
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- Current and emerging strategies for the prevention of hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.International journal of biological sciences · 2024Review
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Article
- Smad7 Deficiency in Myeloid Cells Does Not Affect Liver Injury, Inflammation or Fibrosis after Chronic CClInternational journal of molecular sciences · 2021Article
- TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer.Gastroenterology · 2021Review
- MiR-21-3p Promotes Hepatocellular Carcinoma ProgressionFrontiers in oncology · 2021Article
- Article
- Acute Liver Injury after CClInternational journal of molecular sciences · 2019Article
- Review
- Hepatectomy promotes recurrence of liver cancer by enhancing IL-11-STAT3 signaling.EBioMedicine · 2019Article
- miR-181b-induced SMAD7 downregulation controls granulosa cell apoptosis through TGF-β signaling by interacting with the TGFBR1 promoter.Journal of cellular physiology · 2018Article
Corrections and comments
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Authors and funding
16 authors.
Funding
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Abstract
TGF-β signaling in liver cells has variant roles in the dynamics of liver diseases, including hepatocellular carcinoma (HCC). We previously found a correlation of high levels of the important endogenous negative TGF-β signaling regulator SMAD7 with better clinical outcome in HCC patients. However, the underlying tumor-suppressive molecular mechanisms are still unclear. Here, we show that conditional (TTR-Cre) hepatocyte-specific SMAD7 knockout (KO) mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine (DEN) challenge, verifying SMAD7 as a tumor suppressor in HCC. In line with our findings in patients, Smad7 levels in both tumor tissue as well as surrounding tissue show a significant inverse correlation with tumor numbers. SMAD7 KO mice presented with increased pSMAD2/3 levels and decreased apoptosis in the tumor tissue. Higher tumor incidence was accompanied by reduced P21 and upregulated c-MYC expression in the tumors. Activation of signal transducer and activator of transcription factor 3 signaling was found in Smad7-deficient mouse tumors and in patients with low tumoral SMAD7 expression as compared with surrounding tissue. Together, our results provide new mechanistic insights into the tumor-suppressive functions of SMAD7 in hepatocarcinogenesis.
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Registered trials
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