ArticleInternational journal of biological sciences2023
TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression.
Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Association between NDRG1 protein expression and aggressive features of breast cancer: a systematic review and meta-analysis.BMC cancer · 2023Pooled it
- Editorial: Exploiting non-oncogene addiction for overcoming drug resistance in metastatic tumors.Frontiers in pharmacology · 2026Article
- Insight into the Regulation of NDRG1 Expression.International journal of molecular sciences · 2025Review
- Signature-based repurposed drugs resemble the inhibition of TGFβ-induced NDRG1 as potential therapeutics for triple-negative breast cancer.International journal of biological sciences · 2025Article
- Unraveling the protein kinase C/NDRG1 signaling network in breast cancer.Cell & bioscience · 2024Article
- Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy.Molecular cancer · 2024Article
- NDRGs in Breast Cancer: A Review and In Silico Analysis.Cancers · 2024Review
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- The Role of NDRG1 Expression in Vasculogenic Mimicry of High-grade Gliomas.Journal of Cancer · 2024Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.
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