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01-02-2015 | Research Paper

HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer

Authors: Ruixue Yuan, Jia Ke, Lei Sun, Zhen He, Yifeng Zou, Xiaosheng He, Yufeng Chen, Xianrui Wu, Zerong Cai, Lei Wang, Jianping Wang, Xinjuan Fan, Xiaojian Wu, Ping Lan

Published in: Clinical & Experimental Metastasis | Issue 2/2015

Abstract

Hairy enhancer of split-1 (HES1) is a transcriptional target of the Notch pathway, and a high level of HES1 is regarded as a marker of activated Notch. The aim of the study was to investigate the role of HES1 in colorectal cancer progression. We used tissue microarrays to analyze the expression and clinical significance of HES1 in 320 colorectal cancer samples. Stable overexpression and knockdown of HES1 were established in three colorectal cancer cell (CRC) lines (RKO, HCT8 and LOVO). We investigated the differentially expressed genes and enriched pathways in HES1 overexpressing CRC cells by gene expression profiling. Also, the role of HES1 in invasion and migration were examined in vitro and in vivo. We found that high expression of HES1 was significantly correlated with distal metastasis (P = 0.037) at diagnosis, and HES1 could serve as an unfavorable prognostic factor for colorectal cancer patients (P = 0.034). Gene expression profiling and pathway enrichment analysis revealed that HES1 was related to cellular adherens junction loss. In addition, we showed that HES1 overexpression lead to depressed E-cadherin, and elevated N-cadherin, vimentin and Twist-1 levels. Functionally, HES1 enhanced invasiveness and metastasis of CRC cells. HES1 promotes cancer metastasis via inducing epithelial mesenchymal transition and serves as a poor prognosis factor of colorectal cancer patients.

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Title: HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer
Authors: Ruixue Yuan
Jia Ke
Lei Sun
Zhen He
Yifeng Zou
Xiaosheng He
Yufeng Chen
Xianrui Wu
Zerong Cai
Lei Wang
Jianping Wang
Xinjuan Fan
Xiaojian Wu
Ping Lan
Publication date: 01-02-2015
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 2/2015
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-015-9700-y

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