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

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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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Acknowledgments

Supported by National Natural Science Foundation of China (Nos. 81072046, 91029702, 81402019), 985 project of Sun Yat-sen University, Guangdong Translational Medicine Public Platform (4202037), and Guangdong Department of Science & Technology Translational Medicine Center Grant (2011A080300002). We thank Bart Westendorp kindly for revision of the manuscript.

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The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Rd, Guangzhou, 510642, Guangdong, People’s Republic of China

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

    2. Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

      Xinjuan Fan

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    Ruixue Yuan, Jia Ke and Lei Sun have contributed equally to this work.

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    Yuan, R., Ke, J., Sun, L. et al. HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer. Clin Exp Metastasis 32, 169–179 (2015). https://doi.org/10.1007/s10585-015-9700-y

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