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Multi-proteomic and transcriptomic analysis of oncogenic β-catenin molecular networks

Multi-proteomic and transcriptomic analysis of oncogenic β-catenin molecular networks
Multi-proteomic and transcriptomic analysis of oncogenic β-catenin molecular networks
Dys-regulation of Wnt signalling is a frequent occurrence in many different cancers. Oncogenic mutations of CTNNB1/β-catenin, the key nuclear effector of canonical Wnt signalling, lead to accumulation and stabilization of β-catenin protein with diverse effects in cancer cells. Although the transcriptional response to Wnt/β-catenin signaling activation has been widely studied, an integrated understanding of the effects of oncogenic β-catenin on molecular networks is lacking. We used Affinity-Purification Mass-Spectrometry (AP-MS), label-free LC-MS/MS and RNA-Seq to compare protein-protein interactions, protein expression and gene-expression in colorectal cancer cells expressing mutant/oncogenic or wild-type β-catenin. We generate an integrated molecular network and use it to identify novel protein modules that are associated with mutant or wild-type β-catenin. We identify a DNA methyltransferase I (DNMT1) associated sub-network that is enriched in cells with mutant β-catenin and a sub-network enriched in wild-type cells associated with the CDKN2A tumor suppressor linking these processes to transformation of colorectal cancer cells through oncogenic β-catenin signaling. In summary, multi-omics analysis of a defined colorectal cancer cell model provides for a significantly more comprehensive identification of functional molecular networks associated with oncogenic β-catenin signaling.
1535-3893
2216-2225
Ewing, Rob M.
022c5b04-da20-4e55-8088-44d0dc9935ae
Song, Jing
c3f6ccf2-4c63-487c-9c39-e25382b9ee91
Gokulrangan, Giridharan
dfe5f205-72aa-4e41-b11b-5155ef82c9ad
Bai, Sheldon
8559e272-9b1e-4107-a244-991a1869e683
Bowler, Emily H.
af2391ca-58c3-4b8b-b31b-2a7751577bd8
Bolton, Rachel
ef622c55-8cf1-46e0-b3dd-97c967dce111
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Wang, Zhenghe
9142416c-1981-4fa6-9fd7-e0a61a81fc33
Ewing, Rob M.
022c5b04-da20-4e55-8088-44d0dc9935ae
Song, Jing
c3f6ccf2-4c63-487c-9c39-e25382b9ee91
Gokulrangan, Giridharan
dfe5f205-72aa-4e41-b11b-5155ef82c9ad
Bai, Sheldon
8559e272-9b1e-4107-a244-991a1869e683
Bowler, Emily H.
af2391ca-58c3-4b8b-b31b-2a7751577bd8
Bolton, Rachel
ef622c55-8cf1-46e0-b3dd-97c967dce111
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Wang, Zhenghe
9142416c-1981-4fa6-9fd7-e0a61a81fc33

Ewing, Rob M., Song, Jing, Gokulrangan, Giridharan, Bai, Sheldon, Bowler, Emily H., Bolton, Rachel, Skipp, Paul, Wang, Yihua and Wang, Zhenghe (2018) Multi-proteomic and transcriptomic analysis of oncogenic β-catenin molecular networks. Journal of Proteome Research, 17 (6), 2216-2225. (doi:10.1021/acs.jproteome.8b00180).

Record type: Article

Abstract

Dys-regulation of Wnt signalling is a frequent occurrence in many different cancers. Oncogenic mutations of CTNNB1/β-catenin, the key nuclear effector of canonical Wnt signalling, lead to accumulation and stabilization of β-catenin protein with diverse effects in cancer cells. Although the transcriptional response to Wnt/β-catenin signaling activation has been widely studied, an integrated understanding of the effects of oncogenic β-catenin on molecular networks is lacking. We used Affinity-Purification Mass-Spectrometry (AP-MS), label-free LC-MS/MS and RNA-Seq to compare protein-protein interactions, protein expression and gene-expression in colorectal cancer cells expressing mutant/oncogenic or wild-type β-catenin. We generate an integrated molecular network and use it to identify novel protein modules that are associated with mutant or wild-type β-catenin. We identify a DNA methyltransferase I (DNMT1) associated sub-network that is enriched in cells with mutant β-catenin and a sub-network enriched in wild-type cells associated with the CDKN2A tumor suppressor linking these processes to transformation of colorectal cancer cells through oncogenic β-catenin signaling. In summary, multi-omics analysis of a defined colorectal cancer cell model provides for a significantly more comprehensive identification of functional molecular networks associated with oncogenic β-catenin signaling.

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acs.jproteome.8b00180 - Accepted Manuscript
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More information

Accepted/In Press date: 10 May 2018
e-pub ahead of print date: 10 May 2018
Published date: 2018

Identifiers

Local EPrints ID: 421030
URI: http://eprints.soton.ac.uk/id/eprint/421030
ISSN: 1535-3893
PURE UUID: 46eb8fad-f061-4c5d-8ca7-d775c383d302
ORCID for Rob M. Ewing: ORCID iD orcid.org/0000-0001-6510-4001
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

Catalogue record

Date deposited: 21 May 2018 16:30
Last modified: 22 Nov 2021 06:24

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Contributors

Author: Rob M. Ewing ORCID iD
Author: Jing Song
Author: Giridharan Gokulrangan
Author: Sheldon Bai
Author: Emily H. Bowler
Author: Rachel Bolton
Author: Paul Skipp ORCID iD
Author: Yihua Wang ORCID iD
Author: Zhenghe Wang

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