ArticleCancer research2014
Definition of smad3 phosphorylation events that affect malignant and metastatic behaviors in breast cancer cells.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Concurrent Inhibition of AKT and GLUT1 Reveals Endpoint-Specific Effects on Glucose Metabolism and Cell Death in HepG2 Hepatocyte-Derived Cells.Biomedicines · 2026Article
- Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.World journal of gastrointestinal oncology · 2024Article
- N-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer.Cell death & disease · 2023Article
- Image-based high-throughput mapping of TGF-β-induced phosphocomplexes at a single-cell level.Communications biology · 2021Article
- Osteoarthritis-Related Inflammation Blocks TGF-β's Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region.International journal of molecular sciences · 2021Article
- The Post-Translational Regulation of Epithelial-Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis.International journal of molecular sciences · 2021Review
- Identification of Hub Genes and Key Pathways Associated with Anti-Biomolecules · 2021Article
- The Relationship Between Single Nucleotide Polymorphisms ofPharmacogenomics and personalized medicine · 2020Article
- Review
- MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts.BMB reports · 2019Article
- Phosphorylation status at Smad3 linker region modulates transforming growth factor-β-induced epithelial-mesenchymal transition and cancer progression.Cancer science · 2019Review
- Extracellular vesicles derived from cancer-associated fibroblasts induce the migration and invasion of oral squamous cell carcinoma.Journal of extracellular vesicles · 2019Article
- Palbociclib enhances activin-SMAD-induced cytostasis in estrogen receptor-positive breast cancer.Cancer science · 2019Article
- Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation.Journal of cancer prevention · 2018Article
- Regulation of Hematopoiesis and Hematological Disease by TGF-β Family Signaling Molecules.Cold Spring Harbor perspectives in biology · 2017Review
- Article
- Posttranslational Regulation of Smads.Cold Spring Harbor perspectives in biology · 2016Review
- Carcinogen 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis is accelerated in Smad3 heterozygous mice compared to Smad3 wild type mice.Oncotarget · 2016Article
- Krüppel-like factor 17, a novel tumor suppressor: its low expression is involved in cancer metastasis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration.Cell cycle (Georgetown, Tex.) · 2016Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Smad3, a major intracellular mediator of TGFβ signaling, functions as both a positive and negative regulator in carcinogenesis. In response to TGFβ, the TGFβ receptor phosphorylates serine residues at the Smad3 C-tail. Cancer cells often contain high levels of the MAPK and CDK activities, which can lead to the Smad3 linker region becoming highly phosphorylated. Here, we report, for the first time, that mutation of the Smad3 linker phosphorylation sites markedly inhibited primary tumor growth, but significantly increased lung metastasis of breast cancer cell lines. In contrast, mutation of the Smad3 C-tail phosphorylation sites had the opposite effect. We show that mutation of the Smad3 linker phosphorylation sites greatly intensifies all TGFβ-induced responses, including growth arrest, apoptosis, reduction in the size of putative cancer stem cell population, epithelial-mesenchymal transition, and invasive activity. Moreover, all TGFβ responses were completely lost on mutation of the Smad3 C-tail phosphorylation sites. Our results demonstrate a critical role of the counterbalance between the Smad3 C-tail and linker phosphorylation in tumorigenesis and metastasis. Our findings have important implications for therapeutic intervention of breast cancer.
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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.