ArticleMolecular and cellular biology2005
Smad4 dependency defines two classes of transforming growth factor {beta} (TGF-{beta}) target genes and distinguishes TGF-{beta}-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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Who cites it
174 citing papers in PubMed, 338 citations in OpenAlex.
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- Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib.Journal of clinical medicine · 2025Review
- An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.Journal of virology · 2025Article
- Threading the Needle: Navigating Novel Immunotherapeutics in Pancreatic Ductal Adenocarcinoma.Cancers · 2025Review
- Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review.Frontiers in endocrinology · 2025Review
- Gut microbiota dysbiosis impairs TGF-β/Smad4 signaling to drive postoperative metastasis in colorectal cancer.Frontiers in microbiology · 2025Article
- CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation.The Biochemical journal · 2024Article
- Article
- TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
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- Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.Discover oncology · 2024Review
- Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes.PLoS pathogens · 2024Article
- Machine learning unveils RNA polymerase II binding as a predictor for SMAD2-dependent transcription dynamics in response to Actvin signalling.IET systems biology · 2024Article
- The TGF-β superfamily as potential therapeutic targets in pancreatic cancer.Frontiers in oncology · 2024Review
- Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer.Frontiers in oncology · 2024Review
- Opposing USP19 splice variants in TGF-β signaling and TGF-β-induced epithelial-mesenchymal transition of breast cancer cells.Cellular and molecular life sciences : CMLS · 2023Article
- ST3GAL5-catalyzed gangliosides inhibit TGF-β-induced epithelial-mesenchymal transition via TβRI degradation.The EMBO journal · 2023Article
- Multiomics of Colorectal Cancer Organoids Reveals Putative Mediators of Cancer Progression Resulting from SMAD4 Inactivation.Journal of proteome research · 2023Article
- Epithelial-intrinsic defects in TGFβR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis.Science immunology · 2023Article
- SMAD2/3 mediate oncogenic effects of TGF-β in the absence of SMAD4.Communications biology · 2022Article
114 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to transforming growth factor beta (TGF-beta), Smad4 forms complexes with activated Smad2 and Smad3, which accumulate in the nucleus, where they both positively and negatively regulate TGF-beta target genes. Mutation or deletion of Smad4 is found in about 50% of pancreatic tumors and in about 15% of colorectal tumors. As Smad4 is a central component of the TGF-beta/Smad pathway, we have determined whether Smad4 is absolutely required for all TGF-beta responses, to evaluate the effect of its loss during human tumor development. We have generated cell lines from the immortalized human keratinocyte cell line HaCaT or the pancreatic tumor cell line Colo-357, which stably express a tetracyline-inducible small interfering RNA targeted against Smad4. In response to tetracycline, Smad4 expression is effectively silenced. Large-scale microarray analysis identifies two populations of TGF-beta target genes that are distinguished by their dependency on Smad4. Some genes absolutely require Smad4 for their regulation, while others do not. Functional analysis also indicates a differential Smad4 requirement for TGF-beta-induced functions; TGF-beta-induced cell cycle arrest and migration, but not epithelial-mesenchymal transition, are abolished after silencing of Smad4. Altogether our results suggest that loss of Smad4 might promote TGF-beta-mediated tumorigenesis by abolishing tumor-suppressive functions of TGF-beta while maintaining some tumor-promoting TGF-beta responses.
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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.