ArticleGenes & cancer2019
Increased Smad3 and reduced Smad2 levels mediate the functional switch of TGF-β from growth suppressor to growth and metastasis promoter through TMEPAI/PMEPA1 in triple negative breast cancer.
Article in Genes & cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- TMEPAI Confers Paclitaxel Resistance in Triple-Negative Breast Cancer Cells by Promoting AKT Phosphorylation and Its Downstream Cascade.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Downregulation of SMAD2 and SMAD4 is associated with poor prognosis and shorter survival in esophageal squamous cell carcinoma.Molecular biology reports · 2025Article
- Heterogeneity analysis and prognostic model construction of HPV negative oral squamous cell carcinoma T cells using ScRNA-seq and bulk-RNA analysis.Functional & integrative genomics · 2025Article
- Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC.JHEP reports : innovation in hepatology · 2024Article
- miRNAs in Signal Transduction of SMAD Proteins in Breast Cancer.International journal of molecular sciences · 2024Article
- Targeted therapy approaches for epithelial-mesenchymal transition in triple negative breast cancer.Frontiers in oncology · 2024Review
- Loss of the receptors ER, PR and HER2 promotes USP15-dependent stabilization of PARP1 in triple-negative breast cancer.Nature cancer · 2023Article
- Prostate transmembrane androgen inducible protein 1Frontiers in oncology · 2023Review
- A STAT5-Smad3 dyad regulates adipogenic plasticity of visceral adipose mesenchymal stromal cells during chronic inflammation.NPJ Regenerative medicine · 2022Article
- CRISPR/Cas9 system in breast cancer therapy: advancement, limitations and future scope.Cancer cell international · 2022Review
- Long noncoding RNA Smyca coactivates TGF-β/Smad and Myc pathways to drive tumor progression.Journal of hematology & oncology · 2022Article
- Article
- Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis.Cellular and molecular bioengineering · 2022Review
- Age-related DNA methylation in paired normal and tumour breast tissue in Chinese breast cancer patients.Epigenetics · 2021Article
- Combination of Fish Oil and Selenium Enhances Anticancer Efficacy and Targets Multiple Signaling Pathways in Anti-VEGF Agent Treated-TNBC Tumor-Bearing Mice.Marine drugs · 2021Article
- ATAD2 interacts with C/EBPβ to promote esophageal squamous cell carcinoma metastasis via TGF-β1/Smad3 signaling.Journal of experimental & clinical cancer research : CR · 2021Article
- Potential Effect ofBiomolecules · 2021Article
- TGF-β-Induced TMEPAI Promotes Epithelial-Mesenchymal Transition in Doxorubicin-Treated Triple-Negative Breast Cancer Cells via SMAD3 and PI3K/AKT Pathway Alteration.Breast cancer (Dove Medical Press) · 2021Article
- CRISPR/Cas9 based genome editing for targeted transcriptional control in triple-negative breast cancer.Computational and structural biotechnology journal · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Screening of several TNBC cell lines showed altered Smad2 and Smad3 protein levels compared to normal mammary epithelial cells, suggesting the possibility that it could play an important role in the escape of cancer cells from TGF-β mediated growth inhibition. To assess the functional relevance of these endogenous molecules, Smad2 or Smad3 expression was knocked down individually and assessed their effects on pro-oncogenic properties of TGF-β. Smad3 deficiency reduced growth and invasion capacity of breast cancer cells in comparison to Smad2 which had no effect. Smad3 deficiency was also found to be associated with a reduction in the expressions of TMEPAI/PMEPA1 and EMT inducing transcription factors, E-Cadherin and increased expression of cell cycle inhibitors and Vimentin. On the other hand, Smad2 deficiency had opposite effect on these regulators. Interestingly, the decreased growth, invasion and associated gene expressions were largely reversed by overexpressing TMEPAI in Smad3 knockdown cells, suggesting that Smad3-TMEPAI axis may be involved in subverting growth suppressive effects of TGF-β into growth promotion. Similarly, altered levels of Smad proteins and TMEPAI were also noted in primary TNBC tumor tissues. Analysis of the existing databases provided additional support in terms of TMEPAI and Smad2 expression impacting the survival of TNBC patients. Taken together, our data demonstrate a novel role for Smad3 in cancer transformation and cancer progression through TMEPAI and further suggest that selective targeting of TGF-β-Smad3-TMEPAI axis may be beneficial in triple negative breast cancer therapy and prevention.
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