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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Breast Neoplasms / metabolism*
  • Caspase 3 / metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Female
  • Focal Adhesion Kinase 1 / biosynthesis
  • Focal Adhesions / metabolism
  • Gene Knockdown Techniques
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Nuclear Proteins / biosynthesis
  • Paxillin / biosynthesis
  • Signal Transduction
  • Smad Proteins / metabolism*
  • Snail Family Transcription Factors
  • Transcription Factors / biosynthesis
  • Twist-Related Protein 1 / biosynthesis


  • Bone Morphogenetic Proteins
  • Cell Adhesion Molecules, Neuronal
  • Nuclear Proteins
  • Paxillin
  • RGMB protein, human
  • SNAI1 protein, human
  • Smad Proteins
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • JNK Mitogen-Activated Protein Kinases
  • Caspase 3