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

doi:10.1038/s41598-018-24982-z

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^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-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 language	English
Article number	7522
Pages (from-to)	7522
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-24982-z
Publication status	Published - 14 May 2018

Funding

This study was supported by National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, Netherlands Organisation for Scientific Research (NWO grant 612.001.203), and Dutch Cancer Society (KWF Fellowship 2013-5885).

Funders	Funder number
Dutch Cancer Society
Guy’s and St Thomas’ NHS Foundation Trust
King’s College London
National Institute for Health Research
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	612.001.203
KWF Kankerbestrijding	2013-5885

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41598-018-24982-z

Persistent URL (handle)

Copy link address

Cite this

Jacobsen, A., Bosch, L. J. W., Martens-De Kemp, S. R., Carvalho, B., Sillars-Hardebol, A. H., Dobson, R. J., De Rinaldis, E., Meijer, G. A., Abeln, S., Heringa, J., Fijneman, R. J. A., & Feenstra, K. A. (2018). Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. Scientific Reports, 8(1), 7522. Article 7522. https://doi.org/10.1038/s41598-018-24982-z

@article{ae153655921c49f98756c70a3e4dca04,

title = "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 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.",

author = "Annika Jacobsen and Bosch, {Linda J.W.} and {Martens-De Kemp}, {Sanne R.} and Beatriz Carvalho and Sillars-Hardebol, {Anke H.} and Dobson, {Richard J.} and {De Rinaldis}, Emanuele and Meijer, {Gerrit A.} and Sanne Abeln and Jaap Heringa and Fijneman, {Remond J.A.} and Feenstra, {K. Anton}",

year = "2018",

month = may,

day = "14",

doi = "10.1038/s41598-018-24982-z",

language = "English",

volume = "8",

pages = "7522",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

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

TY - JOUR

T1 - Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer

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.

AU - De Rinaldis, Emanuele

AU - Meijer, Gerrit A.

AU - Abeln, Sanne

AU - Heringa, Jaap

AU - Fijneman, Remond J.A.

AU - Feenstra, K. Anton

PY - 2018/5/14

Y1 - 2018/5/14

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85047014115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047014115&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-24982-z

DO - 10.1038/s41598-018-24982-z

M3 - Article

C2 - 29760449

SN - 2045-2322

VL - 8

SP - 7522

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 7522

ER -

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

Abstract

Funding

UN SDGs

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this