ArticleOncogene2015
SMAD4 exerts a tumor-promoting role in hepatocellular carcinoma.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Developing a strain-dependent susceptibility to hepatocellular carcinoma in a murine model based on histopathological evidence and genetic context.Animal models and experimental medicine · 2026Article
- THe Biom: a platform for visualization and exploration of cancer transcriptomic biomarkers identified by robust feature selection.Bioinformatics advances · 2026Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Review
- Article
- SMAD4 enhances the cytotoxic efficacy of human NK cells against colorectal cancer cells via the mFrontiers in immunology · 2024Article
- The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.International journal of biological sciences · 2024Review
- Hepatocyte-specific Smad4 deficiency inhibits hepatocarcinogenesis by promoting CXCL10/CXCR3-dependent CD8Theranostics · 2024Article
- Therapeutic effect and transcriptome-methylome characteristics of METTL3 inhibition in liver hepatocellular carcinoma.Cancer cell international · 2023Article
- PPM1H is down-regulated by ATF6 and dephosphorylates p-RPS6KB1 to inhibit progression of hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2023Article
- Hepatocyte-Specific Smad4 Deficiency Alleviates Liver Fibrosis via the p38/p65 Pathway.International journal of molecular sciences · 2022Article
- Circulating microRNAs (miR-16, miR-22, miR-122) expression and early diagnosis of hepatocellular carcinoma.Journal of clinical laboratory analysis · 2022Article
- Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy.World journal of stem cells · 2022Review
- SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway.Cancer cell international · 2022Article
- Identification of a TGF-β/SMAD/lnc-UTGF positive feedback loop and its role in hepatoma metastasis.Signal transduction and targeted therapy · 2021Article
- SLC38A4 functions as a tumour suppressor in hepatocellular carcinoma through modulating Wnt/β-catenin/MYC/HMGCS2 axis.British journal of cancer · 2021Article
- Structural based screening of potential inhibitors of SMAD4: a step towards personalized medicine for gall bladder and other associated cancers.Molecular diversity · 2021Article
- mRNA-miRNA-lncRNA Regulatory Network in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Article
- miR-224 Regulates the Aggressiveness of Hepatoma Cells Through the IL-6/STAT3/SMAD4 Pathway.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Article
- Proteomic Profiling and Artificial Intelligence for Hepatocellular Carcinoma Translational Medicine.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Further understanding of the molecular biology and pathogenesis of hepatocellular carcinoma (HCC) is crucial for future therapeutic development. SMAD4, recognized as an important tumor suppressor, is a central mediator of transforming growth factor beta (TGFB) and bone morphogenetic protein (BMP) signaling. This study investigated the role of SMAD4 in HCC. Nuclear localization of SMAD4 was observed in a cohort of 140 HCC patients using tissue microarray. HCC cell lines were used for functional assay in vitro and in immune-deficient mice. Nuclear SMAD4 levels were significantly increased in patient HCC tumors as compared with adjacent tissues. Knockdown of SMAD4 significantly reduced the efficiency of colony formation and migratory capacity of HCC cells in vitro and was incompatible with HCC tumor initiation and growth in mice. Knockdown of SMAD4 partially conferred resistance to the anti-growth effects of BMP ligand in HCC cells. Importantly, simultaneous elevation of SMAD4 and phosphorylated SMAD2/3 is significantly associated with poor patient outcome after surgery. Although high levels of SMAD4 can also mediate an antitumor function by coupling with phosphorylated SMAD1/5/8, this signaling, however, is absent in majority of our HCC patients. In conclusion, this study revealed a highly non-canonical tumor-promoting function of SMAD4 in HCC. The drastic elevation of nuclear SMAD4 in sub-population of HCC tumors highlights its potential as an outcome predictor for patient stratification and a target for personalized therapeutic development.
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