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J Cell Biochem. 2012 Jul;113(7):2523-31. doi: 10.1002/jcb.24128.

Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling.

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  • 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.

Copyright © 2012 Wiley Periodicals, Inc.

[PubMed - indexed for MEDLINE]
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