ArticleGastroenterology2010
Antimetastatic role of Smad4 signaling in colorectal cancer.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review.Molecular biology reports · 2021Pooled it
- TGF-β/SMAD4/14-3-3σ/TFEB axis promotes mesenchymal-epithelial transition and inhibits autophagy in colorectal cancer.Cell death & disease · 2026Article
- Genomics correlates of brain metastasis and progression in colorectal cancer.Neuro-oncology · 2025Article
- Forward genetic screening in engineered colorectal cancer organoids identifies regulators of metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SMAD4 mutation drives gut microbiome shifts toward tumor progression in colorectal cancer.Discover oncology · 2025Article
- The Lyn/RUVBL1 Complex Promotes Colorectal Cancer Liver Metastasis by Regulating Arachidonic Acid Metabolism Through Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 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
- Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review.World journal of gastrointestinal oncology · 2024Article
- In Vitro Cytotoxicity of Fluorinated Quaternary Ammonium Salts in Colorectal Cancer Cells and In Silico Pharmacology.Advances in pharmacological and pharmaceutical sciences · 2024Article
- In Vitro Organoid-Based Assays Reveal SMAD4 Tumor-Suppressive Mechanisms for Serrated Colorectal Cancer Invasion.Cancers · 2023Article
- Article
- Proactive and reactive roles of TGF-β in cancer.Seminars in cancer biology · 2023Review
- BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells.World journal of gastroenterology · 2023Article
- Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review.World journal of gastrointestinal surgery · 2023Review
- TheCancers · 2023Article
- Intertumoral Differences Dictate the Outcome of TGF-β Blockade on the Efficacy of Viro-Immunotherapy.Cancer research communications · 2023Article
- ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Search for New Participants in the Pathogenesis of High-Grade Serous Ovarian Cancer with the Potential to Be Used as Diagnostic Molecules.Life (Basel, Switzerland) · 2022Article
- CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.Current issues in molecular biology · 2022Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsTransforming growth factor (TGF)-beta signaling occurs through Smads 2/3/4, which translocate to the nucleus to regulate transcription; TGF-beta has tumor-suppressive effects in some tumor models and pro-metastatic effects in others. In patients with colorectal cancer (CRC), mutations or reduced levels of Smad4 have been correlated with reduced survival. However, the function of Smad signaling and the effects of TGF-beta-receptor kinase inhibitors have not been analyzed during CRC metastasis. We investigated the role of TGF-beta/Smad signaling in CRC progression.
methodsWe evaluated the role of TGF-beta/Smad signaling on cell proliferation, migration, invasion, tumorigenicity, and metastasis in Smad4-null colon carcinoma cell lines (MC38 and SW620) and in those that transgenically express Smad4. We also determined the effects of a TGF-beta-receptor kinase inhibitor (LY2109761) in CRC tumor progression and metastasis in mice.
resultsTGF-beta induced migration/invasion, tumorigenicity, and metastasis of Smad4-null MC38 and SW620 cells; incubation with LY2109761 reversed these effects. In mice, LY2109761 blocked metastasis of CRC cells to liver, inducing cancer cell expression of E-cadherin and reducing the expression of the tumorigenic proteins matrix metalloproteinase-9, nm23, urokinase plasminogen activator, and cyclooxygenase-2. Transgenic expression of Smad4 significantly reduced the oncogenic potential of MC38 and SW620 cells; in these transgenic cells, TGF-beta had tumor suppressor, rather than tumorigenic, effects.
conclusionsTGF-beta/Smad signaling suppresses progression and metastasis of CRC cells and tumors in mice. Loss of Smad4 might underlie the functional shift of TGF-beta from a tumor suppressor to a tumor promoter; inhibitors of TGF-beta signaling might be developed as CRC therapeutics.
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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.