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pubmed, article, nature, google, scholar, tumour, cancer, cas, data, cell, tumours, cells, heterogeneity, clonal, growth, central, extended, polyak, model, access, figure, subclonal, kornelia, evolution, ads, massachusetts, usa, fig, content, subclones, mathematical, cookies, information, marusyk, tumor, boston, initiated, ilrα, privacy, noncellautonomous, altrock, dynamics, institute, research, department, harvard, mixtures, parental, supplementary, doxorubicin,

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nature portfolio permissions reprints privacy policy limit cancer development advertising shannon index author information authors social media stat1 mediate il-11-dependent dana-farber cancer institute wnt-driven mammary cancers nature rev author correspondence nature med human-specific reference amplicon sample kolmogorov–smirnov test fluorescent-activated cell sorting enabling inter-clonal interactions nature 481 nature 501 nature 469 nature 463 nature 508 nature 514 nature springerlink instant access permissions intra-tumour clonal heterogeneity tumour volume–density relation extended data figures total tumour size tumour-growth promoting effects il11-expressing clones derived supplementary references privacy article marusyk green fluorescent protein issue learn metastasis competent subclones competing financial interests 3d culture systems explore content subscription content branched evolution revealed cell-autonomous driving single-cell transcriptomics cell death occurs cell-autonomous mechanism vanessa almendro overcoming environmental constraints

Questions {❓}

• Challenging the axiom: does the occurrence of oncogenic mutations truly limit cancer development with age?
• Why don't we get more cancer?

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      description:Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits. To investigate the role of sub-clonal tumour heterogeneity in cancer progression, a mouse xenograft model was used which revealed that tumour growth can be driven by a minor cell subpopulation by a non-cell-autonomous mechanism, although this minor subpopulation can be outcompeted by faster proliferating competitors. Tumours are often composed of cell populations that differ in their genetic lesions and biological properties, but how such 'sub-clonal' heterogeneity arises and with what consequences on cancer progression is still relatively obscure. Now Kornelia Polyak and colleagues have used a mouse model to show that tumour growth can be driven by a minor cell subpopulation through a non-cell-autonomous mechanism. This minor subpopulation can, however, also be outcompeted by faster proliferating competitors, resulting in tumour collapse. The results illustrate the complexity of sub-clone interactions and clonal interference in heterogeneous tumours, with potential implications for therapy.
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Analytics and Tracking {📊}

• Google Tag Manager

Libraries {📚}

• Prism.js
• Zoom.js

Emails and Hosting {✉️}

Mail Servers:

• mxa-002c5801.gslb.pphosted.com
• mxb-002c5801.gslb.pphosted.com

Name Servers:

• pdns1.ultradns.net
• pdns2.ultradns.net
• pdns3.ultradns.org
• pdns4.ultradns.org
• pdns5.ultradns.info
• pdns6.ultradns.co.uk

CDN Services {📦}

• Crossref