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Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling
Author(s) -
Li Jin,
Ye Lin,
Sanders Andrew J.,
Jiang Wen G.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24128
Subject(s) - gene knockdown , cancer research , microbiology and biotechnology , small hairpin rna , smad , breast cancer , chemistry , cancer cell , signal transduction , cancer , biology , apoptosis , genetics , biochemistry
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. J. Cell. Biochem. 113: 2523–2531, 2012. © 2012 Wiley Periodicals, Inc.