Repulsive Guidance Molecule B (RGMB) Plays Negative Roles in Breast Cancer by Coordinating BMP Signaling
Repulsive Guidance Molecule B (RGMB) Plays Negative Roles in Breast Cancer by Coordinating BMP Signaling
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DOI：
10.1002/jcb.24128
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发表时间：
2012-07-01
影响因子：
4
通讯作者：
Jiang, Wen G.
中科院分区：
文献类型：
--
作者：
Li, Jin;Ye, Lin;Jiang, Wen G.
排斥引导分子（RGM）协调轴突形成和铁稳态。这些分子也被称为骨形态发生蛋白 (BMP) 的共受体。然而，RGM 在乳腺癌中发挥的作用仍不清楚。本研究探讨RGMB对乳腺癌细胞功能的影响及其机制。通过抗RGMB核酶转基因，乳腺癌细胞中的RGMB被敲除。敲除RGMB可增强乳腺癌细胞的增殖、粘附和迁移能力。进一步的研究表明，RGMB 敲低导致 Caspase-3 的表达和活性降低，并伴随着 RGMB 敲低细胞在血清饥饿下更好的存活，这可能是由于其对 MAPK JNK 通路的抑制所致。通过增强 Smad 依赖性信号传导上调 Snail、Twist、FAK 和 Paxillin，从而提高粘附和迁移能力。我们目前的数据首先表明，RGMB 可能通过 BMP 信号传导在乳腺癌中发挥负调节作用。 J.细胞。生物化学。 113：2523-2531，2012。(C)2012 Wiley 期刊公司。
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 Snail, 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. (C) 2012 Wiley Periodicals, Inc.