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ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1

ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1
ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a key step in the transformation of epithelial cells into migratory and invasive tumour cells. Intricate positive and negative regulatory processes regulate EMT. Many oncogenic signalling pathways can induce EMT, but the specific mechanisms of how this occurs, and how this process is controlled are not fully understood.

METHODS: RNA-Seq analysis, computational analysis of protein networks and large-scale cancer genomics datasets were used to identify ELF3 as a negative regulator of the expression of EMT markers. Western blotting coupled to siRNA as well as analysis of tumour/normal colorectal cancer panels was used to investigate the expression and function of ELF3.

RESULTS: RNA-Seq analysis of colorectal cancer cells expressing mutant and wild-type β-catenin and analysis of colorectal cancer cells expressing inducible mutant RAS showed that ELF3 expression is reduced in response to oncogenic signalling and antagonizes Wnt and RAS oncogenic signalling pathways. Analysis of gene-expression patterns across The Cancer Genome Atlas (TCGA) and protein localization in colorectal cancer tumour panels showed that ELF3 expression is anti-correlated with β-catenin and markers of EMT and correlates with better clinical prognosis.

CONCLUSIONS: ELF3 is a negative regulator of the EMT transcription factor (EMT-TF) ZEB1 through its function as an antagonist of oncogenic signalling.

Journal Article
1538-4047
1-11
Liu, D.
3523c58b-432a-4383-91ad-0b29cb66954e
Skomorovska, Y.
205061c8-0a00-4680-87a0-f59169f50535
Song, J.
ff153b32-763b-49cb-846d-a6199b912241
Bowler, E.
af2391ca-58c3-4b8b-b31b-2a7751577bd8
Harris, R.
5d057360-0a9f-4b95-a042-d0884292ff2d
Ravasz, M.
5b885584-6234-43ea-93e5-48ee7fde2317
Bai, S.
91e9bb33-da7d-4316-beb7-1e774032c2ba
Ayati, M.
642cd8f9-df99-4843-bdd2-0222226289e0
Tamai, K.
0ce67de9-008f-46cf-8e61-f4ad5dc46806
Koyuturk, M.
4320991e-860d-4599-b32e-e438e4d8bad5
Yuan, X.
0a8d8c22-c4c8-40c7-aa44-0ea876d51872
Wang, Z.
46165ad0-5411-4850-af80-2b92686089db
Wang, Y.
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Ewing, R.M.
022c5b04-da20-4e55-8088-44d0dc9935ae
Liu, D.
3523c58b-432a-4383-91ad-0b29cb66954e
Skomorovska, Y.
205061c8-0a00-4680-87a0-f59169f50535
Song, J.
ff153b32-763b-49cb-846d-a6199b912241
Bowler, E.
af2391ca-58c3-4b8b-b31b-2a7751577bd8
Harris, R.
5d057360-0a9f-4b95-a042-d0884292ff2d
Ravasz, M.
5b885584-6234-43ea-93e5-48ee7fde2317
Bai, S.
91e9bb33-da7d-4316-beb7-1e774032c2ba
Ayati, M.
642cd8f9-df99-4843-bdd2-0222226289e0
Tamai, K.
0ce67de9-008f-46cf-8e61-f4ad5dc46806
Koyuturk, M.
4320991e-860d-4599-b32e-e438e4d8bad5
Yuan, X.
0a8d8c22-c4c8-40c7-aa44-0ea876d51872
Wang, Z.
46165ad0-5411-4850-af80-2b92686089db
Wang, Y.
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Ewing, R.M.
022c5b04-da20-4e55-8088-44d0dc9935ae

Liu, D., Skomorovska, Y., Song, J., Bowler, E., Harris, R., Ravasz, M., Bai, S., Ayati, M., Tamai, K., Koyuturk, M., Yuan, X., Wang, Z., Wang, Y. and Ewing, R.M. (2018) ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1. Cancer Biology & Therapy, 1-11. (doi:10.1080/15384047.2018.1507256).

Record type: Article

Abstract

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a key step in the transformation of epithelial cells into migratory and invasive tumour cells. Intricate positive and negative regulatory processes regulate EMT. Many oncogenic signalling pathways can induce EMT, but the specific mechanisms of how this occurs, and how this process is controlled are not fully understood.

METHODS: RNA-Seq analysis, computational analysis of protein networks and large-scale cancer genomics datasets were used to identify ELF3 as a negative regulator of the expression of EMT markers. Western blotting coupled to siRNA as well as analysis of tumour/normal colorectal cancer panels was used to investigate the expression and function of ELF3.

RESULTS: RNA-Seq analysis of colorectal cancer cells expressing mutant and wild-type β-catenin and analysis of colorectal cancer cells expressing inducible mutant RAS showed that ELF3 expression is reduced in response to oncogenic signalling and antagonizes Wnt and RAS oncogenic signalling pathways. Analysis of gene-expression patterns across The Cancer Genome Atlas (TCGA) and protein localization in colorectal cancer tumour panels showed that ELF3 expression is anti-correlated with β-catenin and markers of EMT and correlates with better clinical prognosis.

CONCLUSIONS: ELF3 is a negative regulator of the EMT transcription factor (EMT-TF) ZEB1 through its function as an antagonist of oncogenic signalling.

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Accepted CBT 2018 - Accepted Manuscript
Restricted to Repository staff only until 27 August 2019.
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More information

Accepted/In Press date: 29 July 2018
e-pub ahead of print date: 27 August 2018
Keywords: Journal Article

Identifiers

Local EPrints ID: 423836
URI: https://eprints.soton.ac.uk/id/eprint/423836
ISSN: 1538-4047
PURE UUID: bb8e6b98-ed8e-4f74-95e2-a6ef1c1b0731
ORCID for Y. Wang: ORCID iD orcid.org/0000-0001-5561-0648
ORCID for R.M. Ewing: ORCID iD orcid.org/0000-0001-6510-4001

Catalogue record

Date deposited: 02 Oct 2018 16:30
Last modified: 20 Jul 2019 00:41

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Contributors

Author: D. Liu
Author: Y. Skomorovska
Author: J. Song
Author: E. Bowler
Author: R. Harris
Author: M. Ravasz
Author: S. Bai
Author: M. Ayati
Author: K. Tamai
Author: M. Koyuturk
Author: X. Yuan
Author: Z. Wang
Author: Y. Wang ORCID iD
Author: R.M. Ewing ORCID iD

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