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dc.contributor.authorTrigos, AS
dc.contributor.authorPearson, RB
dc.contributor.authorPapenfuss, AT
dc.contributor.authorGoode, DL
dc.date.accessioned2020-12-18T03:40:15Z
dc.date.available2020-12-18T03:40:15Z
dc.date.issued2018-01-23
dc.identifierpii: bjc2017398
dc.identifier.citationTrigos, A. S., Pearson, R. B., Papenfuss, A. T. & Goode, D. L. (2018). How the evolution of multicellularity set the stage for cancer. BRITISH JOURNAL OF CANCER, 118 (2), pp.145-152. https://doi.org/10.1038/bjc.2017.398.
dc.identifier.issn0007-0920
dc.identifier.urihttp://hdl.handle.net/11343/255869
dc.description.abstractNeoplastic growth and many of the hallmark properties of cancer are driven by the disruption of molecular networks established during the emergence of multicellularity. Regulatory pathways and molecules that evolved to impose regulatory constraints upon networks established in earlier unicellular organisms enabled greater communication and coordination between the diverse cell types required for multicellularity, but also created liabilities in the form of points of vulnerability in the network that when mutated or dysregulated facilitate the development of cancer. These factors are usually overlooked in genomic analyses of cancer, but understanding where vulnerabilities to cancer lie in the networks of multicellular species would provide important new insights into how core molecular processes and gene regulation change during tumourigenesis. We describe how the evolutionary origins of genes influence their roles in cancer, and how connections formed between unicellular and multicellular genes that act as key regulatory hubs for normal tissue homeostasis can also contribute to malignant transformation when disrupted. Tumours in general are characterised by increased dependence on unicellular processes for survival, and major dysregulation of the control structures imposed on these processes during the evolution of multicellularity. Mounting molecular evidence suggests altered interactions at the interface between unicellular and multicellular genes play key roles in the initiation and progression of cancer. Furthermore, unicellular network regions activated in cancer show high degrees of robustness and plasticity, conferring increased adaptability to tumour cells by supporting effective responses to environmental pressures such as drug exposure. Examining how the links between multicellular and unicellular regions get disrupted in tumours has great potential to identify novel drivers of cancer, and to guide improvements to cancer treatment by identifying more effective therapeutic strategies. Recent successes in targeting unicellular processes by novel compounds underscore the logic of such approaches. Further gains could come from identifying genes at the interface between unicellular and multicellular processes and manipulating the communication between network regions of different evolutionary ages.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHow the evolution of multicellularity set the stage for cancer
dc.typeJournal Article
dc.identifier.doi10.1038/bjc.2017.398
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleBritish Journal of Cancer
melbourne.source.volume118
melbourne.source.issue2
melbourne.source.pages145-152
melbourne.identifier.nhmrc1052904
melbourne.identifier.nhmrc1053792
dc.rights.licenseCC BY
melbourne.elementsid1300856
melbourne.contributor.authorGoode, David
melbourne.contributor.authorPearson, Richard
melbourne.contributor.authorPapenfuss, Anthony
dc.identifier.eissn1532-1827
melbourne.identifier.fundernameidNHMRC, 1052904
melbourne.identifier.fundernameidNHMRC, 1053792
melbourne.accessrightsOpen Access


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