Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness.
Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness.
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DOI：
10.1038/s41467-023-41906-2
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发表时间：
2023-10-07
影响因子：
16.6
通讯作者：
Pilosof, Shai
中科院分区：
文献类型：
--
作者：
Galai, Geut;He, Xie;Rotblat, Barak;Pilosof, Shai
癌细胞改变代谢酶的表达水平以促进增殖。伴侣是代谢重编程的中心枢纽，伴侣为数百名客户提供服务，形成伴侣-客户互动网络。网络结构如何影响其对分子伴侣靶向的鲁棒性是开发癌症特异性药物治疗的关键。然而，很少有研究评估不同癌症组织的结构和稳健性如何变化。在这里，使用生态网络分析，我们揭示了一个非随机的，分层的模式，癌症类型调节伴侣的能力，实现他们潜在的客户端的相互作用。尽管伴侣-客户互动网络之间的相似性很低，但我们高度准确地预测了一种癌症类型与另一种癌症类型的联系。此外，我们确定了与类似客户互动的伴侣组。网络鲁棒性的模拟表明，这组结构影响癌症特异性的反应伴侣去除。我们的研究结果为关于伴侣-客户相互作用网络的生态学和进化的新假设打开了大门，并可以为癌症特异性药物开发策略提供信息。癌症环境如何改变蛋白质相互作用是一个悬而未决的问题。Galai等人发现了癌症类型调节伴侣-客户相互作用的分层模式，并且他们确定了影响癌症特异性对伴侣损失的反应的结构。
Cancer cells alter the expression levels of metabolic enzymes to fuel proliferation. The mitochondrion is a central hub of metabolic reprogramming, where chaperones service hundreds of clients, forming chaperone-client interaction networks. How network structure affects its robustness to chaperone targeting is key to developing cancer-specific drug therapy. However, few studies have assessed how structure and robustness vary across different cancer tissues. Here, using ecological network analysis, we reveal a non-random, hierarchical pattern whereby the cancer type modulates the chaperones’ ability to realize their potential client interactions. Despite the low similarity between the chaperone-client interaction networks, we highly accurately predict links in one cancer type based on another. Moreover, we identify groups of chaperones that interact with similar clients. Simulations of network robustness show that this group structure affects cancer-specific response to chaperone removal. Our results open the door for new hypotheses regarding the ecology and evolution of chaperone-client interaction networks and can inform cancer-specific drug development strategies. How the cancer environment alters protein interactions is an open question. Galai et al. find a hierarchical pattern whereby cancer type modulates chaperone-client interactions, and they identify structures affecting cancer-specific responses to chaperone loss.
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影响因子：
8.9
作者：
Huang, J;Ling, CX
通讯作者：
Ling, CX
影响因子：
4
作者：
Aguade-Gorgorio, Guim;Costa, Jose;Sole, Ricard
通讯作者：
Sole, Ricard
影响因子：
8.8
作者：
Allesina, Stefano;Pascual, Mercedes
通讯作者：
Pascual, Mercedes
影响因子：
4.1
作者：
Dujon AM;Aktipis A;Alix-Panabières C;Amend SR;Boddy AM;Brown JS;Capp JP;DeGregori J;Ewald P;Gatenby R;Gerlinger M;Giraudeau M;Hamede RK;Hansen E;Kareva I;Maley CC;Marusyk A;McGranahan N;Metzger MJ;Nedelcu AM;Noble R;Nunney L;Pienta KJ;Polyak K;Pujol P;Read AF;Roche B;Sebens S;Solary E;Staňková K;Swain Ewald H;Thomas F;Ujvari B
通讯作者：
Ujvari B
影响因子：
5.2
作者：
Galai, Geut;Ben-David, Hila;Rotblat, Barak
通讯作者：
Rotblat, Barak