ArticleThe Journal of clinical investigation2014
Sustained activation of SMAD3/SMAD4 by FOXM1 promotes TGF-β-dependent cancer metastasis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 170 citations in OpenAlex.
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- The role of FOXM1 in tumor immunology: implications for cancer treatment strategies.Human cell · 2026Review
- The Regulatory Network of FOXM1: Orchestrating Cancer Progression and Resistance to Therapy.International journal of molecular sciences · 2026Review
- OTUD5-TIF1γ-SMAD3/4 positive feedback loop inhibits TGF-β-induced EMT and metastasis in NSCLC.Cell death & disease · 2026Article
- A FoxM1/Smad4 positive feedback loop promotes pancreatic cancer progression.Cell death & disease · 2026Article
- FOXM1 induces therapy resistance and inhibits apoptosis in a variety of human cancers.Cell death & disease · 2026Review
- CCN5 negatively regulates TGF-β-induced endometriosis associated fibrosis through Wnt/β-catenin signaling via Smad3-dependent mechanism.Journal of translational medicine · 2025Article
- Pathogenesis and current status of the treatment of lung cancer associated with idiopathic pulmonary fibrosis.Respiratory research · 2025Review
- Therapeutic Landscape of FOXM1 in Triple-Negative Breast Cancer and Aggressive Solid Cancers.Cancers · 2024Review
- TRIM33 promotes glycolysis through regulating P53 K48-linked ubiquitination to promote esophageal squamous cell carcinoma growth.Cell death & disease · 2024Article
- TGF-β1-Induced LINC01094 promotes epithelial-mesenchymal transition in hepatocellular carcinoma through the miR-122-5p/TGFBR2-SAMD2-SMAD3 Axis.Functional & integrative genomics · 2024Article
- Unravelling the therapeutic potential of forkhead box proteins in breast cancer: An update (Review).Oncology reports · 2024Review
- TRIM33 Is a Co-Regulator of Estrogen Receptor Alpha.Cancers · 2024Article
- Role of circular RNAs in lung cancer.Frontiers in genetics · 2024Review
- Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12.Cell death & disease · 2023Article
- Development of an interfering peptide M1-20 with potent anti-cancer effects by targeting FOXM1.Cell death & disease · 2023Article
- GATA2 co-opts TGFβ1/SMAD4 oncogenic signaling and inherited variants at 6q22 to modulate prostate cancer progression.Journal of experimental & clinical cancer research : CR · 2023Article
- Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer.The pharmacogenomics journal · 2023Article
- FOXM1: A small fox that makes more tracks for cancer progression and metastasis.Seminars in cancer biology · 2023Review
- Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer.Breast cancer research : BCR · 2023Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
A key feature of TGF-β signaling activation in cancer cells is the sustained activation of SMAD complexes in the nucleus; however, the drivers of SMAD activation are poorly defined. Here, using human and mouse breast cancer cell lines, we found that oncogene forkhead box M1 (FOXM1) interacts with SMAD3 to sustain activation of the SMAD3/SMAD4 complex in the nucleus. FOXM1 prevented the E3 ubiquitin-protein ligase transcriptional intermediary factor 1 γ (TIF1γ) from binding SMAD3 and monoubiquitinating SMAD4, which stabilized the SMAD3/SMAD4 complex. Loss of FOXM1 abolished TGF-β-induced SMAD3/SMAD4 formation. Moreover, the interaction of FOXM1 and SMAD3 promoted TGF-β/SMAD3-mediated transcriptional activity and target gene expression. We found that FOXM1/SMAD3 interaction was required for TGF-β-induced breast cancer invasion, which was the result of SMAD3/SMAD4-dependent upregulation of the transcription factor SLUG. Importantly, the function of FOXM1 in TGF-β-induced invasion was not dependent on FOXM1's transcriptional activity. Knockdown of SMAD3 diminished FOXM1-induced metastasis. Furthermore, FOXM1 levels correlated with activated TGF-β signaling and metastasis in human breast cancer specimens. Together, our data indicate that FOXM1 promotes breast cancer metastasis by increasing nuclear retention of SMAD3 and identify crosstalk between FOXM1 and TGF-β/SMAD3 pathways. This study highlights the critical interaction of FOXM1 and SMAD3 for controlling TGF-β signaling during metastasis.
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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.