Widespread Rewiring of Genetic Networks upon Cancer Signaling Pathway Activation.
Widespread Rewiring of Genetic Networks upon Cancer Signaling Pathway Activation.
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DOI：
10.1016/j.cels.2017.10.015
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发表时间：
2018-01-24
期刊：
影响因子：
9.3
通讯作者：
Boutros M
中科院分区：
文献类型：
--
作者：
Billmann M;Chaudhary V;ElMaghraby MF;Fischer B;Boutros M
细胞信号网络协调所有多细胞生物的生理过程。在网络内，模块切换其功能来控制信号活动以响应细胞环境。 然而，一直缺乏绘制这些模块相互作用的系统方法。在这里，我们生成了后生动物信号通路的上下文相关遗传相互作用网络。使用果蝇中的 Wnt 信号传导作为模型，在被 Wnt 配体激活后或在肿瘤抑制因子 APC 丢失后，我们在基线状态下测量了超过 290,000 次该通路的双重扰动。我们发现 Wnt 网络内的遗传相互作用在通路激活后全局重新连接。我们推导了状态间网络，显示基因如何在特定状态网络之间改变其功能。这种相关通路抑制剂跨状态并确定了通路激活所需的基因。例如，我们预测并证实了 ER 驻留蛋白 Catsup 是配体介导的 Wnt 信号传导激活所必需的。状态依赖性和状态间遗传相互作用网络共同识别控制细胞途径的响应功能模块。三种细胞状态下 Wnt 信号传导的遗传相互作用网络 通过配体激活 Wnt 通路或通过丢失 APC 来重新连接网络 相互作用图谱识别已知和新颖的状态依赖性通路模块 状态特异性和状态间图谱相似性识别信号调节因子 在通路激活之前和之后对 Wnt 通路组分之间的遗传相互作用进行系统测量，揭示该通路如何在扰动时重新连接。
Cellular signaling networks coordinate physiological processes in all multicellular organisms. Within networks, modules switch their function to control signaling activity in response to the cellular context. However, systematic approaches to map the interplay of such modules have been lacking. Here, we generated a context-dependent genetic interaction network of a metazoan's signaling pathway. Using Wnt signaling in Drosophila as a model, we measured >290,000 double perturbations of the pathway in a baseline state, after activation by Wnt ligand or after loss of the tumor suppressor APC. We found that genetic interactions within the Wnt network globally rewired after pathway activation. We derived between-state networks that showed how genes changed their function between state-specific networks. This related pathway inhibitors across states and identified genes required for pathway activation. For instance, we predicted and confirmed the ER-resident protein Catsup to be required for ligand-mediated Wnt signaling activation. Together, state-dependent and between-state genetic interaction networks identify responsive functional modules that control cellular pathways. Genetic interaction networks of Wnt signaling in three cellular states Networks rewire upon activation of Wnt pathway by ligand or by loss of APC Interaction profiles identify known and novel state-dependent pathway modules State-specific and between-state profile similarity identify signaling regulators Systematic measurement of genetic interactions between components of the Wnt pathway before and after pathway activation reveals how the pathway is rewired upon perturbation.
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影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
16
作者：
Guénolé A;Srivas R;Vreeken K;Wang ZZ;Wang S;Krogan NJ;Ideker T;van Attikum H
通讯作者：
van Attikum H
在基因组量表上对酵母中适应性和遗传相互作用的定量分析。
影响因子：
48
作者：
Baryshnikova, Anastasia;Costanzo, Michael;Kim, Yungil;Ding, Huiming;Koh, Judice;Toufighi, Kiana;Youn, Ji-Young;Ou, Jiongwen;San Luis, Bryan-Joseph;Bandyopadhyay, Sunayan;Hibbs, Matthew;Hess, David;Gingras, Anne-Claude;Bader, Gary D.;Troyanskaya, Olga G.;Brown, Grant W.;Andrews, Brenda;Boone, Charles;Myers, Chad L.
通讯作者：
Myers, Chad L.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
64.5
作者：
Azzolin, Luca;Zanconato, Francesca;Piccolo, Stefano
通讯作者：
Piccolo, Stefano