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

• Published in: Scientific reports Vol. 8; no. 1; pp. 7522 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.05.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/89; 45; 45/61; 631/114/2391; 631/114/2404; 631/67/1504/1885; 692/4028/67/1504/1885; 692/4028/67/69; Adenoma; Algorithms; Aurora kinase; Aurora Kinase A - genetics; Aurora Kinase A - metabolism; Caco-2 Cells; Carcinogenesis; Cell Line, Tumor; Chromosomes, Human, Pair 20 - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Deregulation; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene Regulatory Networks; Humanities and Social Sciences; Humans; MAP kinase; MAP Kinase Signaling System; multidisciplinary; Protein interaction; Protein Interaction Maps; Ras protein; ras Proteins - metabolism; Science; Science (multidisciplinary); Signal transduction; Tumor cell lines; Wnt protein; Wnt Signaling Pathway; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-24982-z

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.