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
1-11
Liu, D.
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Skomorovska, Y.
205061c8-0a00-4680-87a0-f59169f50535
Song, J.
ff153b32-763b-49cb-846d-a6199b912241
Bowler, E.
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Harris, R.
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Ravasz, M.
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Bai, S.
91e9bb33-da7d-4316-beb7-1e774032c2ba
Ayati, M.
642cd8f9-df99-4843-bdd2-0222226289e0
Tamai, K.
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Koyuturk, M.
4320991e-860d-4599-b32e-e438e4d8bad5
Yuan, X.
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Wang, Z.
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Wang, Y.
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Ewing, R.M.
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Liu, D.
fa317aa7-0f6d-4d60-9329-4b476debd724
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, .
(doi:10.1080/15384047.2018.1507256).
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.
Text
Accepted CBT 2018
- Accepted Manuscript
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Accepted/In Press date: 29 July 2018
e-pub ahead of print date: 27 August 2018
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Journal Article
Identifiers
Local EPrints ID: 423836
URI: http://eprints.soton.ac.uk/id/eprint/423836
ISSN: 1538-4047
PURE UUID: bb8e6b98-ed8e-4f74-95e2-a6ef1c1b0731
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Date deposited: 02 Oct 2018 16:30
Last modified: 16 Mar 2024 07:02
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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
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