N-Myc Downstream-Regulated Genes in Cancer Metastasis
Summary
N-Myc is a transcription factor often amplified in aggressive tumours. Its downstream-regulated genes, notably the NDRG family (N-myc downstream-regulated genes 1–4), play pivotal roles in the metastatic cascade. Among these, NDRG1 functions as a context-dependent metastasis suppressor or, paradoxically, an oncogene in certain tumour subtypes. It modulates epithelial-mesenchymal transition (EMT), cell migration, invasion and intracellular lipid handling. NDRG2 and NDRG3 have also emerged as regulators of cell adhesion and survival under stress. Mechanistically, these proteins influence key signalling pathways, including TGF-β, PI3K/AKT and ErbB receptor networks, often via phosphorylation or protein–protein interactions. Their expression can be regulated by hypoxia, iron availability and transforming-growth-factor stimuli. Clinically, NDRG1 levels correlate with patient outcome across multiple cancer types, offering promise as both a prognostic biomarker and a therapeutic target. Emerging strategies involve selective iron chelators, small-molecule inhibitors and combination regimens that restore or inhibit NDRG function, with the aim of preventing metastatic dissemination and overcoming drug resistance.
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N-Myc Downstream-Regulated Genes in Cancer Metastasis publication trend
The graph below shows the total number of articles in n-myc downstream-regulated genes in cancer metastasis across all publications each year (not limited to Nature Index journals).
Technical terms
Metastasis suppressor: A gene whose expression inhibits spread of cancer cells without necessarily affecting primary tumour growth.
Epithelial-mesenchymal transition (EMT): A cellular programme in which epithelial cells acquire migratory mesenchymal properties, facilitating invasion.
Phosphorylation: A reversible post-translational modification involving addition of a phosphate group, often modulating protein activity.
Cancer stem cells (CSCs): A subpopulation of tumour cells with self-renewal capacity and resistance to standard therapies, implicated in relapse.
Iron chelator: A molecule that binds free iron, altering iron-dependent signalling pathways such as those controlling NDRG gene expression.
References
- TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression. International Journal of Biological Sciences (2023).
- NDRG1 acts as an oncogene in triple-negative breast cancer and its loss sensitizes cells to mitochondrial iron chelation. Frontiers in Pharmacology (2024).
- Antimetastatic Activity of Apoptolidin A by Upregulation of N-Myc Downstream-Regulated Gene 1 Expression in Human Colorectal Cancer Cells. Pharmaceuticals (2023).
- NDRG1 regulates neutral lipid metabolism in breast cancer cells. Breast Cancer Research (2018).
- Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling. Journal of Biological Chemistry (2017).
- The Iron Chelators Dp44mT and DFO Inhibit TGF-β-induced Epithelial-Mesenchymal Transition via Up-Regulation of N-Myc Downstream-regulated Gene 1 (NDRG1). Journal of Biological Chemistry (2012).
- The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways*. Journal of Biological Chemistry (2015).
- Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer. Oncotarget (2015).
- Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers. BMC Genomic Data (2004).
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