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RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer

BACKGROUND: Runt-related transcription factor 1 (RUNX1) plays the roles of an oncogene and an anti-oncogene in epithelial tumours, and abnormally elevated RUNX1 has been suggested to contribute to the carcinogenesis of colorectal cancer (CRC). However, the mechanism remains unclear. METHODS: The exp...

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Autores principales: Li, Qingyuan, Lai, Qiuhua, He, Chengcheng, Fang, Yuxin, Yan, Qun, Zhang, Yue, Wang, Xinke, Gu, Chuncai, Wang, Yiqing, Ye, Liangying, Han, Lu, Lin, Xin, Chen, Junsheng, Cai, Jianqun, Li, Aimin, Liu, Side
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670220/
https://www.ncbi.nlm.nih.gov/pubmed/31370857
http://dx.doi.org/10.1186/s13046-019-1330-9
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author Li, Qingyuan
Lai, Qiuhua
He, Chengcheng
Fang, Yuxin
Yan, Qun
Zhang, Yue
Wang, Xinke
Gu, Chuncai
Wang, Yiqing
Ye, Liangying
Han, Lu
Lin, Xin
Chen, Junsheng
Cai, Jianqun
Li, Aimin
Liu, Side
author_facet Li, Qingyuan
Lai, Qiuhua
He, Chengcheng
Fang, Yuxin
Yan, Qun
Zhang, Yue
Wang, Xinke
Gu, Chuncai
Wang, Yiqing
Ye, Liangying
Han, Lu
Lin, Xin
Chen, Junsheng
Cai, Jianqun
Li, Aimin
Liu, Side
author_sort Li, Qingyuan
collection PubMed
description BACKGROUND: Runt-related transcription factor 1 (RUNX1) plays the roles of an oncogene and an anti-oncogene in epithelial tumours, and abnormally elevated RUNX1 has been suggested to contribute to the carcinogenesis of colorectal cancer (CRC). However, the mechanism remains unclear. METHODS: The expression of RUNX1 in CRC and normal tissues was detected by real-time quantitative PCR and Western blotting. The effect of RUNX1 on CRC migration and invasion was conducted by functional experiments in vitro and in vivo. Chromatin Immunoprecipitation assay verified the direct regulation of RUNX1 on the promoter of the KIT, which leads to the activation of Wnt/β-catenin signaling. RESULTS: RUNX1 expression is upregulated in CRC tissues. Upregulated RUNX1 promotes cell metastasis and epithelial to mesenchymal transition (EMT) of CRC both in vitro and in vivo. Furthermore, RUNX1 can activate Wnt/β-catenin signalling in CRC cells by directly interacting with β-catenin and targeting the promoter and enhancer regions of KIT to promote KIT transcription. These observations demonstrate that RUNX1 upregulation is a common event in CRC specimens and is closely correlated with cancer metastasis and that RUNX1 promotes EMT of CRC cells by activating Wnt/β-catenin signalling. Moreover, RUNX1 is regulated by Wnt/β-catenin. CONCLUSION: Our findings first demonstrate that RUNX1 promotes CRC metastasis by activating the Wnt/β-catenin signalling pathway and EMT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1330-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-66702202019-08-06 RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer Li, Qingyuan Lai, Qiuhua He, Chengcheng Fang, Yuxin Yan, Qun Zhang, Yue Wang, Xinke Gu, Chuncai Wang, Yiqing Ye, Liangying Han, Lu Lin, Xin Chen, Junsheng Cai, Jianqun Li, Aimin Liu, Side J Exp Clin Cancer Res Research BACKGROUND: Runt-related transcription factor 1 (RUNX1) plays the roles of an oncogene and an anti-oncogene in epithelial tumours, and abnormally elevated RUNX1 has been suggested to contribute to the carcinogenesis of colorectal cancer (CRC). However, the mechanism remains unclear. METHODS: The expression of RUNX1 in CRC and normal tissues was detected by real-time quantitative PCR and Western blotting. The effect of RUNX1 on CRC migration and invasion was conducted by functional experiments in vitro and in vivo. Chromatin Immunoprecipitation assay verified the direct regulation of RUNX1 on the promoter of the KIT, which leads to the activation of Wnt/β-catenin signaling. RESULTS: RUNX1 expression is upregulated in CRC tissues. Upregulated RUNX1 promotes cell metastasis and epithelial to mesenchymal transition (EMT) of CRC both in vitro and in vivo. Furthermore, RUNX1 can activate Wnt/β-catenin signalling in CRC cells by directly interacting with β-catenin and targeting the promoter and enhancer regions of KIT to promote KIT transcription. These observations demonstrate that RUNX1 upregulation is a common event in CRC specimens and is closely correlated with cancer metastasis and that RUNX1 promotes EMT of CRC cells by activating Wnt/β-catenin signalling. Moreover, RUNX1 is regulated by Wnt/β-catenin. CONCLUSION: Our findings first demonstrate that RUNX1 promotes CRC metastasis by activating the Wnt/β-catenin signalling pathway and EMT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1330-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-01 /pmc/articles/PMC6670220/ /pubmed/31370857 http://dx.doi.org/10.1186/s13046-019-1330-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Li, Qingyuan
Lai, Qiuhua
He, Chengcheng
Fang, Yuxin
Yan, Qun
Zhang, Yue
Wang, Xinke
Gu, Chuncai
Wang, Yiqing
Ye, Liangying
Han, Lu
Lin, Xin
Chen, Junsheng
Cai, Jianqun
Li, Aimin
Liu, Side
RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
title RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
title_full RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
title_fullStr RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
title_full_unstemmed RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
title_short RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
title_sort runx1 promotes tumour metastasis by activating the wnt/β-catenin signalling pathway and emt in colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670220/
https://www.ncbi.nlm.nih.gov/pubmed/31370857
http://dx.doi.org/10.1186/s13046-019-1330-9
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