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

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...

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Autores principales:	Annika Jacobsen, Linda J. W. Bosch, Sanne R. Martens-de Kemp, Beatriz Carvalho, Anke H. Sillars-Hardebol, Richard J. Dobson, Emanuele de Rinaldis, Gerrit A. Meijer, Sanne Abeln, Jaap Heringa, Remond J. A. Fijneman, K. Anton Feenstra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dda70b65d4554e6cb45b72de811ecbd1
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spelling	oai:doaj.org-article:dda70b65d4554e6cb45b72de811ecbd12021-12-02T11:41:25ZAurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer10.1038/s41598-018-24982-z2045-2322https://doaj.org/article/dda70b65d4554e6cb45b72de811ecbd12018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24982-zhttps://doaj.org/toc/2045-2322Abstract 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.Annika JacobsenLinda J. W. BoschSanne R. Martens-de KempBeatriz CarvalhoAnke H. Sillars-HardebolRichard J. DobsonEmanuele de RinaldisGerrit A. MeijerSanne AbelnJaap HeringaRemond J. A. FijnemanK. Anton FeenstraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annika Jacobsen Linda J. W. Bosch Sanne R. Martens-de Kemp Beatriz Carvalho Anke H. Sillars-Hardebol Richard J. Dobson Emanuele de Rinaldis Gerrit A. Meijer Sanne Abeln Jaap Heringa Remond J. A. Fijneman K. Anton Feenstra Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
description	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.
format	article
author	Annika Jacobsen Linda J. W. Bosch Sanne R. Martens-de Kemp Beatriz Carvalho Anke H. Sillars-Hardebol Richard J. Dobson Emanuele de Rinaldis Gerrit A. Meijer Sanne Abeln Jaap Heringa Remond J. A. Fijneman K. Anton Feenstra
author_facet	Annika Jacobsen Linda J. W. Bosch Sanne R. Martens-de Kemp Beatriz Carvalho Anke H. Sillars-Hardebol Richard J. Dobson Emanuele de Rinaldis Gerrit A. Meijer Sanne Abeln Jaap Heringa Remond J. A. Fijneman K. Anton Feenstra
author_sort	Annika Jacobsen
title	Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
title_short	Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
title_full	Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
title_fullStr	Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
title_full_unstemmed	Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
title_sort	aurora kinase a (aurka) interaction with wnt and ras-mapk signalling pathways in colorectal cancer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/dda70b65d4554e6cb45b72de811ecbd1
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Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer

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