Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.
Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.
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DOI：
10.1016/j.ccr.2014.03.017
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发表时间：
2014-05-12
期刊：
影响因子：
50.3
通讯作者：
Abate-Shen C
中科院分区：
文献类型：
--
作者：
Aytes A;Mitrofanova A;Lefebvre C;Alvarez MJ;Castillo-Martin M;Zheng T;Eastham JA;Gopalan A;Pienta KJ;Shen MM;Califano A;Abate-Shen C
为了确定前列腺癌恶性肿瘤的调控驱动因素，我们分别从人类肿瘤和基因工程小鼠模型的表达谱中组装了人类和小鼠前列腺癌的全基因组调控网络（相互作用组）。这些相互作用组的跨物种计算分析已经确定FOXM1和CENPF作为前列腺癌恶性肿瘤的协同主调节因子。实验验证表明，FOXM1和CENPF协同作用，促进肿瘤生长，通过协调调节靶基因表达和激活与前列腺癌恶性肿瘤相关的关键信号通路。此外，FOXM1和CENPF的共表达是生存和转移不良的可靠预后指标。因此，全基因组跨物种的调控网络的审讯代表了一个有价值的战略，以确定人类癌症的因果机制。
To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactomes has identified FOXM1 and CENPF as synergistic master regulators of prostate cancer malignancy. Experimental validation shows that FOXM1 and CENPF function synergistically to promote tumor growth, by coordinated regulation of target gene expression and activation of key signaling pathways associated with prostate cancer malignancy. Furthermore, co-expression of FOXM1 and CENPF is a robust prognostic indicator of poor survival and metastasis. Thus, genome-wide cross-species interrogation of regulatory networks represents a valuable strategy to identify causal mechanisms of human cancer.
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DOI：
10.1002/wsbm.1159
发表时间：
2012-07
影响因子：
7.9
作者：
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影响因子：
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作者：
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