A biosystems approach to identify the molecular signaling mechanisms of TMEM30A during tumor migration.
A biosystems approach to identify the molecular signaling mechanisms of TMEM30A during tumor migration.
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一种识别肿瘤迁移过程中 TMEM30A 分子信号传导机制的生物系统方法
DOI：
10.1371/journal.pone.0179900
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wen T
中科院分区：
文献类型：
--
作者：
Wang J;Wang Q;Lu D;Zhou F;Wang D;Feng R;Wang K;Molday R;Xie J;Wen T
细胞迁移在肿瘤的生长和发展中起着重要的作用，了解细胞迁移的分子机制对于开发新的肿瘤治疗方法至关重要。跨膜蛋白30A(TMEM30A)的过表达可启动肿瘤细胞的迁移，但其分子机制尚未见报道。因此，我们建议将计算和实验方法相结合，首先使用a)计算生物学方法预测TMEM30A调控的潜在信号网络，b)我们先前在小鼠组织中的TMEM30A复合体的质谱学结果，以及c)手动从文献中收集的一些迁移相关基因，然后执行包括体外划痕试验和实时定量聚合酶链式反应(QPCR)在内的分子生物学实验，以验证预测网络的可靠性。这些结果验证了在计算信号网络中识别的基因在细胞迁移过程中确实受到TMEM30A的调控，这表明了我们所提出的方法的有效性，并揭示了肿瘤迁移的调控机制，这有助于理解肿瘤侵袭的分子基础。
Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network. The results verify that the genes identified in the computational signaling network are indeed regulated by TMEM30A during cell migration, indicating the effectiveness of our proposed method and shedding light on the regulatory mechanisms underlying tumor migration, which facilitates the understanding of the molecular basis of tumor invasion.