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Updated: May 24, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling
Jin Li1, Lin Ye, Andrew J Sanders
1Metastasis & Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
Abstract:
Repulsive guidance molecules (RGMs) coordinate axon formation and iron homestasis. These molecules are also known as co-receptors of bone morphogenetic proteins (BMPs). However, the role played by RGMs in breast cancer remains unclear. The present study investigated the impact of RGMB on functions of breast cancer cells and corresponding mechanisms. RGMB was knocked down in breast cancer cells by way of an anti-RGMB ribozyme transgene. Knockdown of RGMB resulted in enhanced capacities of proliferation, adhesion, and migration in breast cancer cells. Further investigations demonstrated RGMB knockdown resulted in a reduced expression and activity of Caspase-3, accompanied with better survival in RGMB knockdown cells under serum starvation, which might be induced by its repression on MAPK JNK pathway. Up-regulations of Snai1, Twist, FAK, and Paxillin via enhanced Smad dependent sigaling led to increased capacities of adhesion and migration. Our current data firstly revealed that RGMB may act as a negative regulator in breast cancer through BMP signaling.
Insights
Repulsive guidance molecule B (RGMB) suppresses breast cancer progression. Knocking down RGMB enhances cancer cell proliferation, adhesion, and migration, indicating RGMB
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Repulsive guidance molecules (RGMs) are crucial for axon guidance and iron homeostasis.
- RGMs function as co-receptors for bone morphogenetic proteins (BMPs).
- The specific role of RGMs, particularly RGMB, in breast cancer remains largely unelucidated.
Purpose of the Study:
- To investigate the functional impact of RGMB on breast cancer cell behavior.
- To elucidate the underlying molecular mechanisms by which RGMB influences breast cancer progression.
Main Methods:
- RGMB was downregulated in breast cancer cells using an anti-RGMB ribozyme transgene.
- Assessed cell proliferation, adhesion, and migration capacities.
- Analyzed Caspase-3 activity, MAPK JNK pathway signaling, and Smad-dependent signaling pathways.
Main Results:
- RGMB knockdown significantly enhanced breast cancer cell proliferation, adhesion, and migration.
- RGMB deficiency led to reduced Caspase-3 expression/activity and improved cell survival during serum starvation.
- Upregulation of Snai1, Twist, FAK, and Paxillin via Smad signaling was observed, correlating with increased adhesion and migration.
Conclusions:
- RGMB acts as a negative regulator in breast cancer progression.
- RGMB influences breast cancer cell functions, including proliferation, survival, adhesion, and migration, potentially through BMP signaling.
- These findings highlight RGMB as a potential therapeutic target in breast cancer treatment.
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