Selection-driven tumor evolution with public goods leads to patterns of clonal expansion consistent with neutral growth.
Selection-driven tumor evolution with public goods leads to patterns of clonal expansion consistent with neutral growth.
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DOI：
10.1016/j.isci.2020.101901
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发表时间：
2021-01-22
期刊：
影响因子：
5.8
通讯作者：
Basanta D
中科院分区：
文献类型：
--
作者：
Edwards J;Marusyk A;Basanta D
癌症是生态进化过程的结果，该过程由可遗传的表型多样化推动，并由环境依赖性选择驱动。空间是一种限制生长的关键生态资源，探索这种资源的能力很可能受到强烈选择。使用基于主体的建模，我们探索了以通过细胞外基质屏障的细胞外源性降解获得新空间为中心的表型策略与通过最大化细胞增殖来利用该资源之间的相互作用。虽然细胞增殖是细胞固有的属性，但新进入的空间代表着公共利益，可以使生产者和非生产者受益。我们发现这种相互作用会导致生态演替，从而出现大量、异质且高度增殖的种群。尽管在我们的模拟中，重塑和增殖策略都处于强烈的正选择之下，但它们的相互作用导致了亚克隆结构，可以将其解释为中性进化的证据，从而保证对癌症基因组测序的推论进行谨慎解释。使用基于代理的模型，我们探索了肿瘤在空间中的生态进化动力学。我们检查了两种表型：一种用于进入新空间，一种用于消耗空间。我们在模拟中观察到生态演替，导致肿瘤具有高 ITH 模型明确编码选择，但结果可能会被误解为中性进化理论；癌症系统生物学；癌症
Cancers are the result of eco-evolutionary processes fueled by heritable phenotypic diversification and driven by environmentally dependent selection. Space represents a key growth-limiting ecological resource, the ability to explore this resource is likely under strong selection. Using agent-based modeling, we explored the interplay between phenotypic strategies centered on gaining access to new space through cell-extrinsic degradation of extracellular matrix barriers and the exploitation of this resource through maximizing cell proliferation. While cell proliferation is a cell-intrinsic property, newly accessed space represents a public good, which can benefit both producers and non-producers. We found that this interplay results in ecological succession, enabling emergence of large, heterogeneous, and highly proliferative populations. Even though in our simulations both remodeling and proliferation strategies were under strong positive selection, their interplay led to sub-clonal architecture that could be interpreted as evidence for neutral evolution, warranting cautious interpretation of inferences from sequencing of cancer genomes. Using agent-based models, we explored eco-evolutionary dynamics of tumors in space We examined two phenotypes: one for accessing new space and one for consuming space We observed ecological succession in simulations, resulting in tumors with high ITH Model encodes selection explicitly but results could be misconstrued as neutral Evolutionary Theories; Cancer Systems Biology; Cancer
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影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
64.8
作者：
Marusyk, Andriy;Tabassum, Doris P.;Altrock, Philipp M.;Almendro, Vanessa;Michor, Franziska;Polyak, Kornelia
通讯作者：
Polyak, Kornelia
DOI：
10.1073/pnas.0606053103
发表时间：
2006-09-05
影响因子：
11.1
作者：
Axelrod, Robert;Axelrod, David E.;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.
影响因子：
11.2
作者：
Lloyd MC;Cunningham JJ;Bui MM;Gillies RJ;Brown JS;Gatenby RA
通讯作者：
Gatenby RA
DOI：
10.1056/nejmoa1113205
发表时间：
2012-03-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gerlinger M;Rowan AJ;Horswell S;Math M;Larkin J;Endesfelder D;Gronroos E;Martinez P;Matthews N;Stewart A;Tarpey P;Varela I;Phillimore B;Begum S;McDonald NQ;Butler A;Jones D;Raine K;Latimer C;Santos CR;Nohadani M;Eklund AC;Spencer-Dene B;Clark G;Pickering L;Stamp G;Gore M;Szallasi Z;Downward J;Futreal PA;Swanton C
通讯作者：
Swanton C