ArticleThe Journal of clinical investigation2022
EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- KMT5A-mediated methylation of IRF3 promotes tumor progression through immune suppression.iScience · 2026Article
- Circ_0070190 suppresses the malignant progression of cervical cancer by sponging miR-587.Journal of molecular histology · 2026Article
- Sublytic C5b-9 induces S100A8/A9 expression via SMYD4-dependent SOX7-K159 methylation in the glomerular mesangial cells of Thy-1 nephritis rats.Journal of molecular cell biology · 2026Article
- SMAD4 Palmitoylation Drives a Metabolic-Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
- Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis.Nature cell biology · 2026Article
- The mitochondrial translocation of phosphorylated EZH2 promotes PARP inhibitor resistance in BRCA1-deficient epithelial ovarian cancer.Cell discovery · 2026Article
- The role of epigenetic modifications in cancer-associated fibroblasts.Frontiers in medicine · 2026Review
- Article
- TGFβ1-TNFα-regulated secretion of neutrophil chemokines is independent of epithelial-mesenchymal transition in breast tumor cells.Molecular biology of the cell · 2025Article
- PTMFusionNet: A Deep Learning Approach for Predicting Disease Related Post-translational Modification and Classifying Disease Subtypes.Molecular & cellular proteomics : MCP · 2025Article
- Long noncoding RNA TUG1 promotes chondrosarcoma progression and M2 polarization.Genes & diseases · 2025Article
- 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as potential diagnostic markers for breast cancer.Biomarkers in medicine · 2025Article
- Regulation of histone H3K27 methylation in inflammation and cancer.Molecular biomedicine · 2025Review
- Article
- Multiomic characterization, immunological and prognostic potential of SMAD3 in pan-cancer and validation in LIHC.Scientific reports · 2025Article
- KDM5D histone demethylase mediates p38α inactivation via its enzymatic activity to inhibit cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ZNF8 Orchestrates with Smad3 to Promote Lung Metastasis by Recruiting SMYD3 in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- N6-methyladenosine modification and post-translational modification of epithelial-mesenchymal transition in colorectal cancer.Discover oncology · 2024Review
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SMAD3 plays a central role in cancer metastasis, and its hyperactivation is linked to poor cancer outcomes. Thus, it is critical to understand the upstream signaling pathways that govern SMAD3 activation. Here, we report that SMAD3 underwent methylation at K53 and K333 (K53/K333) by EZH2, a process crucial for cell membrane recruitment, phosphorylation, and activation of SMAD3 upon TGFB1 stimulation. Mechanistically, EZH2-triggered SMAD3 methylation facilitated SMAD3 interaction with its cellular membrane localization molecule (SARA), which in turn sustained SMAD3 phosphorylation by the TGFB receptor. Pathologically, increased expression of EZH2 expression resulted in the accumulation of SMAD3 methylation to facilitate SMAD3 activation. EZH2-mediated SMAD3 K53/K333 methylation was upregulated and correlated with SMAD3 hyperactivation in breast cancer, promoted tumor metastasis, and was predictive of poor survival outcomes. We used 2 TAT peptides to abrogate SMAD3 methylation and therapeutically inhibit cancer metastasis. Collectively, these findings reveal the complicated layers involved in the regulation of SMAD3 activation coordinated by EZH2-mediated SMAD3 K53/K333 methylation to drive cancer metastasis.
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