ArticleOncogene2003
Restoration of SMAD4 by gene therapy reverses the invasive phenotype in pancreatic adenocarcinoma cells.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis.Oncotarget · 2017Pooled it
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- Genome-wide CRISPR Screen Reveals RAB10 as a Synthetic Lethal Gene in Colorectal and Pancreatic Cancers Carrying SMAD4 Loss.Cancer research communications · 2023Article
- Antagonism between Prdm16 and Smad4 specifies the trajectory and progression of pancreatic cancer.The Journal of cell biology · 2023Article
- The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis.Frontiers in immunology · 2022Review
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- Multi-omics landscape and clinical significance of aComputational and structural biotechnology journal · 2022Article
- The use of adenoviral vectors in gene therapy and vaccine approaches.Genetics and molecular biology · 2022Article
- The immunoregulation effect of tumor microenvironment in pancreatic ductal adenocarcinoma.Frontiers in oncology · 2022Review
- Review
- Effects of Smad4 on the expression of caspase‑3 and Bcl‑2 in human gingival fibroblasts cultured on 3D PLGA scaffolds induced by compressive force.International journal of molecular medicine · 2021Article
- Successful Immunotherapy for Pancreatic Cancer in a Patient With TSC2 and SMAD4 Mutations: A Case Report.Frontiers in immunology · 2021Article
- Roles of Smads Family and Alternative Splicing Variants of Smad4 in Different Cancers.Journal of Cancer · 2018Review
- miR-509-5p and miR-1243 increase the sensitivity to gemcitabine by inhibiting epithelial-mesenchymal transition in pancreatic cancer.Scientific reports · 2017Article
- The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance.Journal of clinical medicine · 2017Review
- Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition.Biochemical Society transactions · 2016Review
- Article
- BRCA1 regulates transforming growth factor-β (TGF-β1) signaling through Gadd45a by enhancing the protein stability of Smad4.Molecular oncology · 2015Article
- Insights Into SMAD4 Loss in Pancreatic Cancer From Inducible Restoration of TGF-β Signaling.Molecular endocrinology (Baltimore, Md.) · 2015Article
- MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4.Oncotarget · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SMAD4 is a critical cofactor in signal transduction pathways activated in response to transforming growth factor-beta (TGF-beta)-related ligands, regulating cell growth and differentiation. The roles played by SMAD4 inactivation in tumours highlighted it as a tumour-suppressor gene. However, restoration of the TGF-beta antiproliferative pathway following SMAD4 gene transfer in null-tumour cell lines is controversial. Herein, we report the inhibitory effects of SMAD4 on pancreatic tumour invasion and angiogenesis. Adenoviral transfer of this gene in a panel of SMAD4 homozygous-deleted human pancreatic tumour cell lines restored SMAD4 protein expression and function. Although it did not affect proliferation significantly in vitro, SMAD4 inhibited in vivo tumour growth in immunodeficient mice. In this xenograft setting, differential suppression of tumour growth in vivo was mediated, at least in part, through downregulation of vascular endothelial growth factor and expression of gelatinases. We documented the reduced invasion and angiogenesis histologically and by intravital microscopy, and gained mechanistic insight at the messenger and protein level. Finally, we found a negative reciprocal regulation between SMAD4 and ETS-1. ETS-1 is considered a marker for tumour invasion. Upon SMAD4 deletion, we detected high expression levels of ETS-1 in pancreatic tumour cells, suggesting the shift of the pancreatic tumour toward an invasive phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.