title: HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer.
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.
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Rd, Guangzhou, 510642, Guangdong, People's Republic of China.
authors: Ruixue
authors: R
authors: Yuan
authors: Jia
authors: J
authors: Ke
authors: Lei
authors: L
authors: Sun
authors: Zhen
authors: Z
authors: He
authors: Yifeng
authors: Y
authors: Zou
authors: Xiaosheng
authors: X
authors: He
authors: Yufeng
authors: Y
authors: Chen
authors: Xianrui
authors: X
authors: Wu
authors: Zerong
authors: Z
authors: Cai
authors: Lei
authors: L
authors: Wang
authors: Jianping
authors: J
authors: Wang
authors: Xinjuan
authors: X
authors: Fan
authors: Xiaojian
authors: X
authors: Wu
authors: Ping
authors: P
authors: Lan
mesh_terms: D022005:Adherens Junctions; D000368:Aged; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000401:mortality* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D051880:Receptors, Notch / Q000378:metabolism; D046888:Tissue Array Analysis; D000072056:Transcription Factor HES-1; D016896:Treatment Outcome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human
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