TEAD4 promotes colorectal tumorigenesis via transcriptionally targeting YAP1
| Autor: | Yu Jie Bao, Lu Chen, Chen Yang Yu, Jing-Yuan Fang, Hao Yan Chen, Sheng Li Yang, Jie Hong, Jiayin Tang, Jinxian Chen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adenoma
Male Transcriptional Activation 0301 basic medicine Transcription Genetic Carcinogenesis Colorectal cancer Mice Nude Muscle Proteins Colorectal adenoma Biology medicine.disease_cause 03 medical and health sciences Cell Line Tumor medicine Animals Humans TEAD4 Molecular Biology Adaptor Proteins Signal Transducing Cell Proliferation YAP1 Hippo signaling pathway Gene knockdown Base Sequence Cell growth TEA Domain Transcription Factors YAP-Signaling Proteins Cell Biology Middle Aged Phosphoproteins medicine.disease DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Gene Knockdown Techniques Cancer research Female Neoplasm Recurrence Local Colorectal Neoplasms Reports Protein Binding Signal Transduction Transcription Factors Developmental Biology |
| Zdroj: | Cell Cycle. 17:102-109 |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | TEAD4 (TEA domain family member 4) was recently revealed as an oncogenic character in tumorigenesis. However, its role remains unclear in colorectal tumorigenesis. Here, we firstly found that the expression level of TEAD4 was significantly elevated in clinical samples of colorectal adenomas (CRA) and correlated with the size and histological type of CRA. Moreover, patients with higher TEAD4 expression in normal colon mucosa are more prone to be recurrent after polypectomy. TEAD4 knockdown significantly inhibited colorectal cell proliferation in vitro and suppressed tumor growth in vivo. RNA-seq and GSEA analysis reveals TEAD4 can probably regulate Hippo pathway and further experiment confirm the downstream target gene YAP1. The subsequent ChIP-qPCR and luciferase report assay indicated that TEAD4 regulated YAP1 by direct binding and transcriptional activation. In summary, our study reveals that TEAD4 plays an important tumor-promoting role in colorectal cancer by directly targeting the YAP1, thus we suggests TEAD4 may be used as a novel biomarker in colorectal tumorigenesis and provides TEAD4/YAP1 axis as a potential therapeutic option for colorectal cancer. |
| Databáze: | OpenAIRE |
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