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Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer

Jacobsen, A; Bosch, LJW; Martens-de Kemp, SR; Carvalho, B; Sillars-Hardebol, AH; Dobson, RJ; de Rinaldis, E; ... Feenstra, KA; + view all (2018) Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. Scientific Reports , 8 , Article 7522. 10.1038/s41598-018-24982-z. Green open access

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Abstract

Hyperactivation of Wnt and Ras-MAPK signalling are common events in development of colorectal adenomas. Further progression from adenoma-to-carcinoma is frequently associated with 20q gain and overexpression of Aurora kinase A (AURKA). Interestingly, AURKA has been shown to further enhance Wnt and Ras-MAPK signalling. However, the molecular details of these interactions in driving colorectal carcinogenesis remain poorly understood. Here we first performed differential expression analysis (DEA) of AURKA knockdown in two colorectal cancer (CRC) cell lines with 20q gain and AURKA overexpression. Next, using an exact algorithm, Heinz, we computed the largest connected protein-protein interaction (PPI) network module of significantly deregulated genes in the two CRC cell lines. The DEA and the Heinz analyses suggest 20 Wnt and Ras-MAPK signalling genes being deregulated by AURKA, whereof β-catenin and KRAS occurred in both cell lines. Finally, shortest path analysis over the PPI network revealed eight ‘connecting genes’ between AURKA and these Wnt and Ras-MAPK signalling genes, of which UBE2D1, DICER1, CDK6 and RACGAP1 occurred in both cell lines. This study, first, confirms that AURKA influences deregulation of Wnt and Ras-MAPK signalling genes, and second, suggests mechanisms in CRC cell lines describing these interactions.

Type: Article
Title: Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-018-24982-z
Publisher version: https://doi.org/10.1038/s41598-018-24982-z
Language: English
Additional information: © 2018 Macmillan Publishers Limited, part of Springer Nature. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cancer genomics, Cellular signalling networks, Colorectal cancer, Functional clustering
UCL classification: UCL
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 Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10049374
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