TGFβ诱导乳腺癌上皮细胞向间质转化的综合分子相互作用图。

IF 3.5 2区 生物学 Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Sai Bhavani Gottumukkala, Trivadi Sundaram Ganesan, Anbumathi Palanisamy
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引用次数: 0

摘要

乳腺癌是全球最常见的癌症之一,死亡率很高。转移性乳腺癌(MBC)是癌症的晚期阶段,其特征是一个高度非线性、异质性的过程,涉及众多单一途径和调控相互作用。上皮-间质转化(EMT)是癌细胞利用的一种关键机制。依赖于转化生长因子-β(TGFβ)的信号被认为在乳腺癌晚期促进了 EMT。通过广泛的文献调查,我们绘制了一张 TGFβ 诱导 EMT 的综合调控图谱。所绘制的网络包括 312 个不同物种(蛋白质、基因、RNA、复合物)和 426 个反应(状态转换、核易位、复合物结合和解离)。该图谱是利用细胞设计器按照系统生物学图形符号(SBGN)绘制的,并通过 MINERVA ( http://35.174.227.105:8080/minerva/?id=Metastatic_Breast_Cancer_1 ) 公开发布。虽然 MBC 的完整分子机制尚不清楚,但该图谱捕捉到了 TGFβ 诱导 EMT 促进 MBC 的复杂信号相互作用。随后,利用 CaSQ 将绘制的疾病图谱转化为布尔模型,并使用 Cell Collective 进行分析。这些模拟捕捉到了 TGFβ 诱导 MBC EMT 的已知实验结果。已确定了组装图谱的枢纽调节因子,基于转录组的分析证实了它们在癌症转移中的作用。对该图谱的详细分析可能有助于进一步了解转移性乳腺癌的发展和进程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.

Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.

Breast cancer is one of the prevailing cancers globally, with a high mortality rate. Metastatic breast cancer (MBC) is an advanced stage of cancer, characterised by a highly nonlinear, heterogeneous process involving numerous singling pathways and regulatory interactions. Epithelial-mesenchymal transition (EMT) emerges as a key mechanism exploited by cancer cells. Transforming Growth Factor-β (TGFβ)-dependent signalling is attributed to promote EMT in advanced stages of breast cancer. A comprehensive regulatory map of TGFβ induced EMT was developed through an extensive literature survey. The network assembled comprises of 312 distinct species (proteins, genes, RNAs, complexes), and 426 reactions (state transitions, nuclear translocations, complex associations, and dissociations). The map was developed by following Systems Biology Graphical Notation (SBGN) using Cell Designer and made publicly available using MINERVA ( http://35.174.227.105:8080/minerva/?id=Metastatic_Breast_Cancer_1 ). While the complete molecular mechanism of MBC is still not known, the map captures the elaborate signalling interplay of TGFβ induced EMT-promoting MBC. Subsequently, the disease map assembled was translated into a Boolean model utilising CaSQ and analysed using Cell Collective. Simulations of these have captured the known experimental outcomes of TGFβ induced EMT in MBC. Hub regulators of the assembled map were identified, and their transcriptome-based analysis confirmed their role in cancer metastasis. Elaborate analysis of this map may help in gaining additional insights into the development and progression of metastatic breast cancer.

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来源期刊
NPJ Systems Biology and Applications
NPJ Systems Biology and Applications Mathematics-Applied Mathematics
CiteScore
5.80
自引率
0.00%
发文量
46
审稿时长
8 weeks
期刊介绍: npj Systems Biology and Applications is an online Open Access journal dedicated to publishing the premier research that takes a systems-oriented approach. The journal aims to provide a forum for the presentation of articles that help define this nascent field, as well as those that apply the advances to wider fields. We encourage studies that integrate, or aid the integration of, data, analyses and insight from molecules to organisms and broader systems. Important areas of interest include not only fundamental biological systems and drug discovery, but also applications to health, medical practice and implementation, big data, biotechnology, food science, human behaviour, broader biological systems and industrial applications of systems biology. We encourage all approaches, including network biology, application of control theory to biological systems, computational modelling and analysis, comprehensive and/or high-content measurements, theoretical, analytical and computational studies of system-level properties of biological systems and computational/software/data platforms enabling such studies.
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