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

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

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Article number7522
Pages (from-to)7522
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 14 May 2018

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Aurora Kinase A
Colorectal Neoplasms
Cell Line
Protein Interaction Maps
Genes
Adenoma
Catenins
Carcinogenesis
Proteins
Carcinoma

Cite this

Jacobsen, A., Bosch, L. J. W., Martens-De Kemp, S. R., Carvalho, B., Sillars-Hardebol, A. H., Dobson, R. J., ... Feenstra, K. A. (2018). Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. Scientific Reports, 8(1), 7522. [7522]. https://doi.org/10.1038/s41598-018-24982-z
Jacobsen, Annika ; Bosch, Linda J.W. ; Martens-De Kemp, Sanne R. ; Carvalho, Beatriz ; Sillars-Hardebol, Anke H. ; Dobson, Richard J. ; De Rinaldis, Emanuele ; Meijer, Gerrit A. ; Abeln, Sanne ; Heringa, Jaap ; Fijneman, Remond J.A. ; Feenstra, K. Anton. / Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 7522.
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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.",
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Jacobsen, A, Bosch, LJW, Martens-De Kemp, SR, Carvalho, B, Sillars-Hardebol, AH, Dobson, RJ, De Rinaldis, E, Meijer, GA, Abeln, S, Heringa, J, Fijneman, RJA & Feenstra, KA 2018, 'Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer' Scientific Reports, vol. 8, no. 1, 7522, pp. 7522. https://doi.org/10.1038/s41598-018-24982-z

Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. / Jacobsen, Annika; Bosch, Linda J.W.; Martens-De Kemp, Sanne R.; Carvalho, Beatriz; Sillars-Hardebol, Anke H.; Dobson, Richard J.; De Rinaldis, Emanuele; Meijer, Gerrit A.; Abeln, Sanne; Heringa, Jaap; Fijneman, Remond J.A.; Feenstra, K. Anton.

In: Scientific Reports, Vol. 8, No. 1, 7522, 14.05.2018, p. 7522.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Jacobsen, Annika

AU - Bosch, Linda J.W.

AU - Martens-De Kemp, Sanne R.

AU - Carvalho, Beatriz

AU - Sillars-Hardebol, Anke H.

AU - Dobson, Richard J.

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AU - Meijer, Gerrit A.

AU - Abeln, Sanne

AU - Heringa, Jaap

AU - Fijneman, Remond J.A.

AU - Feenstra, K. Anton

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AB - 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.

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Jacobsen A, Bosch LJW, Martens-De Kemp SR, Carvalho B, Sillars-Hardebol AH, Dobson RJ et al. Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. Scientific Reports. 2018 May 14;8(1):7522. 7522. https://doi.org/10.1038/s41598-018-24982-z