Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer
Background/Aims: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. Methods: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, im...
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Cell Physiol Biochem Press GmbH & Co KG
2018-05-01
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doaj-734b4011d52e47609f423bb5a5fddefc2020-11-24T21:46:51ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-05-0147259060310.1159/000490015490015Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal CancerXiaoting HuangLi XiangYueqiao LiYingying ZhaoHuiqiong ZhuYizhi XiaoMengwei LiuXiaosheng WuZhiqing WangPing JiangHaitao QingQiang ZhangGuangnan LiuWenjing ZhangAimin LiYe ChenSide LiuJide WangBackground/Aims: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. Methods: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. Results: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced “CRC cell” migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. Conclusions: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC.https://www.karger.com/Article/FullText/490015SnailFOXK1Cyr61Colorectal cancerMetastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoting Huang Li Xiang Yueqiao Li Yingying Zhao Huiqiong Zhu Yizhi Xiao Mengwei Liu Xiaosheng Wu Zhiqing Wang Ping Jiang Haitao Qing Qiang Zhang Guangnan Liu Wenjing Zhang Aimin Li Ye Chen Side Liu Jide Wang |
spellingShingle |
Xiaoting Huang Li Xiang Yueqiao Li Yingying Zhao Huiqiong Zhu Yizhi Xiao Mengwei Liu Xiaosheng Wu Zhiqing Wang Ping Jiang Haitao Qing Qiang Zhang Guangnan Liu Wenjing Zhang Aimin Li Ye Chen Side Liu Jide Wang Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer Cellular Physiology and Biochemistry Snail FOXK1 Cyr61 Colorectal cancer Metastasis |
author_facet |
Xiaoting Huang Li Xiang Yueqiao Li Yingying Zhao Huiqiong Zhu Yizhi Xiao Mengwei Liu Xiaosheng Wu Zhiqing Wang Ping Jiang Haitao Qing Qiang Zhang Guangnan Liu Wenjing Zhang Aimin Li Ye Chen Side Liu Jide Wang |
author_sort |
Xiaoting Huang |
title |
Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer |
title_short |
Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer |
title_full |
Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer |
title_fullStr |
Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer |
title_full_unstemmed |
Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer |
title_sort |
snail/foxk1/cyr61 signaling axis regulates the epithelial–mesenchymal transition and metastasis in colorectal cancer |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-05-01 |
description |
Background/Aims: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. Methods: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. Results: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced “CRC cell” migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. Conclusions: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC. |
topic |
Snail FOXK1 Cyr61 Colorectal cancer Metastasis |
url |
https://www.karger.com/Article/FullText/490015 |
work_keys_str_mv |
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