UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling

Berenjeno, IM; Piñeiro, R; Castillo, SD; Pearce, W; McGranahan, N; Dewhurst, SM; Meniel, V; ... Vanhaesebroeck, B; + view all (2017) Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling. Nature Communications , 8 , Article 1773. 10.1038/s41467-017-02002-4. Green open access

[img]
Preview
Text (Published article)
Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling.pdf - ["content_typename_Published version" not defined]

Download (3MB) | Preview
[img]
Preview
Text (Supplementary Information)
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_S1.pdf

Download (3MB) | Preview
[img]
Preview
Text (Description of Additional Supplementary Files)
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_S2.pdf

Download (3MB) | Preview
[img]
Preview
Text
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_S3.pdf

Download (195kB) | Preview
[img] Video (Supplementary Movie 1)
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_Video1.avi

Download (1MB)
[img] Video (Supplementary Movie 2)
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_Video2.avi

Download (8MB)
[img] Video (Supplementary Movie 3)
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_Video3.avi

Download (2MB)
[img] Video (Supplementary Movie 4)
Berenjeno_Oncogenic_PIK3CA_centrosome_amplification_Video4.avi.crdownload

Download (118MB)

Abstract

Mutations in PIK3CA are very frequent in cancer and lead to sustained PI3K pathway activation. The impact of acute expression of mutant PIK3CA during early stages of malignancy is unknown. Using a mouse model to activate the Pik3ca H1047R hotspot mutation in the heterozygous state from its endogenous locus, we here report that mutant Pik3ca induces centrosome amplification in cultured cells (through a pathway involving AKT, ROCK and CDK2/Cyclin E-nucleophosmin) and in mouse tissues, and increased in vitro cellular tolerance to spontaneous genome doubling. We also present evidence that the majority of PIK3CA H1047R mutations in the TCGA breast cancer cohort precede genome doubling. These previously unappreciated roles of PIK3CA mutation show that PI3K signalling can contribute to the generation of irreversible genomic changes in cancer. While this can limit the impact of PI3K-targeted therapies, these findings also open the opportunity for therapeutic approaches aimed at limiting tumour heterogeneity and evolution.

Type: Article
Title: Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-017-02002-4
Publisher version: http://dx.doi.org/10.1038/s41467-017-02002-4
Language: English
Additional information: Copyright © The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/10039779
Downloads since deposit
51Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item