Upregulation of C/EBPα contributes to colorectal cancer growth, metastasis and indicates poor survival outcome

The function and clinical implication of transcription factor CCAAT/enhancer-binding protein α (C/EBPα) in colorectal cancer (CRC) still remains undefined. In fact, C/EBPα has long been considered as a tumor suppressor in hematopoietic system and also found lowly expressed in numerous solid tumors....

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Hauptverfasser: Mi, Lan (VerfasserIn) , Hu, Kai (VerfasserIn) , Wen, Xianzi (VerfasserIn) , Sun, Jing (VerfasserIn) , Wu, Aiwen (VerfasserIn) , Wang, Mingliang (VerfasserIn) , Zheng, Minhua (VerfasserIn) , Zang, Lu (VerfasserIn) , Ji, Jiafu (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: August 1, 2018
In: American journal of cancer research
Year: 2018, Jahrgang: 8, Heft: 8, Pages: 1449-1465
ISSN:2156-6976
Online-Zugang: Volltext
Verfasserangaben:Lan Mi, Kai Hu, Xianzi Wen, Jing Sun, Aiwen Wu, Mingliang Wang, Minhua Zheng, Lu Zang, Jiafu Ji

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520 |a The function and clinical implication of transcription factor CCAAT/enhancer-binding protein α (C/EBPα) in colorectal cancer (CRC) still remains undefined. In fact, C/EBPα has long been considered as a tumor suppressor in hematopoietic system and also found lowly expressed in numerous solid tumors. However, our results here for the first time showed that C/EBPα was unexpectedly upregulated and was an independent prognostic marker for patients with CRC. We therefore aimed to explore the detailed role and mechanisms of C/EBPα in CRC. Our investigation demonstrated that C/EBPα promoted tumor growth both in vitro and in vivo. In addition, suppression of C/EBPα inhibited cell proliferation by inducing G1 phase arrest and inducing apoptosis. Also, C/EBPα enhances CRC cells migration and invasion in vitro as well as metastasis in vivo through regulating EMT. Mechanistically, C/EBPα exerts its oncogenic role by targeting c-Myc/cyclin D1 mediated by β-catenin involved pathway and we provide evidence indicating that cytoplasmic exclusion of C/EBPα might contribute to its oncogenic function in tumor progression. In conclusion, C/EBPα acts as an oncogene in CRC and could be a potential biomarker of colon carcinogenesis. 
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