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Updated: Jun 23, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Bone morphogenetic protein-4 induced by NDRG2 expression inhibits MMP-9 activity in breast cancer cells
Soo-Kyung Shon1, Aeyung Kim, Ji Young Kim
1Department of Biological Science and The Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
Abstract:
In the current study, we examined the function of N-myc downstream-regulated gene 2 (NDRG2) expression in breast cancer cells, especially focusing on the role of bone morphogenetic protein-4 (BMP-4) induced by NDRG2. NDRG2 expression in MDA-MB-231 cells inhibited the mRNA expression of several matrix metalloproteinases (MMPs) and the gelatinolytic activity of MMP-9. Interestingly, a specific induction of active BMP-4 was exclusively observed in MDA-MB-231-NDRG2 cells but not in MDA-MB-231-mock cells. Neutralization of BMP-4 in MDA-MB-231-NDRG2 cells resulted in the rescue of MMP-9 mRNA expression and migration capacity. In addition, treatment with recombinant BMP-4 dramatically suppressed MMP-9 mRNA expression, gelatinolytic MMP-9 activity, migration, and invasion capacity both in MDA-MB-231 and PMA-treated MCF-7 cells. Collectively, our data show that BMP-4 induced by NDRG2 expression inhibits the metastatic potential of breast cancer cells, especially via suppression of MMP-9 activity.
Insights
N-myc downstream-regulated gene 2 (NDRG2) suppresses breast cancer metastasis. NDRG2 induces bone morphogenetic protein-4 (BMP-4), which inhibits matrix metalloproteinase-9 (MMP-9) activity and cell migration.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- N-myc downstream-regulated gene 2 (NDRG2) is implicated in cancer progression.
- Matrix metalloproteinases (MMPs), particularly MMP-9, are key regulators of cancer cell invasion and metastasis.
- Bone morphogenetic protein-4 (BMP-4) signaling pathways are involved in various cellular processes, including cancer.
Purpose of the Study:
- To investigate the functional role of NDRG2 in breast cancer cells.
- To elucidate the relationship between NDRG2, BMP-4, and MMP-9 in breast cancer metastasis.
- To determine the therapeutic potential of targeting the NDRG2-BMP-4 axis.
Main Methods:
- Overexpression of NDRG2 in MDA-MB-231 breast cancer cells.
- Analysis of MMP mRNA expression and MMP-9 gelatinolytic activity.
- BMP-4 induction and neutralization experiments.
- Assessment of cell migration and invasion capacity.
- Treatment with recombinant BMP-4 in different breast cancer cell lines.
Main Results:
- NDRG2 expression significantly inhibited MMP mRNA expression and MMP-9 activity in MDA-MB-231 cells.
- NDRG2 induced the expression of active BMP-4 in these cells.
- BMP-4 neutralization rescued MMP-9 expression and migration.
- Recombinant BMP-4 suppressed MMP-9 activity, migration, and invasion in multiple breast cancer cell lines.
Conclusions:
- NDRG2-induced BMP-4 plays a critical role in suppressing breast cancer cell metastasis.
- The NDRG2-BMP-4 pathway inhibits cancer cell invasion primarily through the suppression of MMP-9 activity.
- Targeting this pathway holds promise for novel breast cancer therapeutic strategies.
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