https://scholars.lib.ntu.edu.tw/handle/123456789/516766
標題: | Diverse targets of β-catenin during the epithelial-mesenchymal transition define cancer stem cells and predict disease relapse | 作者: | Chang Y.-W. Su Y.-J. Hsiao M. Wei K.-C. WEI-HSIN LIN Liang C.-L. Chen S.-C. Lee J.-L. |
公開日期: | 2015 | 出版社: | American Association for Cancer Research Inc. | 卷: | 75 | 期: | 16 | 起(迄)頁: | 3398-3410 | 來源出版物: | Cancer Research | 摘要: | Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that are activated by epithelial-mesenchymal transition (EMT). However, the mechanistic relationship between EMT and the Wnt pathway in CSC is not entirely clear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex, the latter of which then binds to CSC-related gene promoters. Tandem coimmunoprecipitation and re-ChIP experiments with epithelial-type cells further revealed that Sox15 associates with the β-catenin/E-cadherin complex, which then binds to the proximal promoter region of CASP3. Through this mechanism, Twist1 cleavage is triggered to regulate a β-catenin-elicited promotion of the CSC phenotype. During EMT, we documented that Twist1 binding to β-catenin enhanced the transcriptional activity of the β-catenin/TCF4 complex, including by binding to the proximal promoter region of ABCG2, a CSC marker. In terms of clinical application, our definition of a five-gene CSC signature (nuclear β-catenin High/nuclear Twist1 High/E-cadherin Low/Sox15Low/CD133High) may provide a useful prognostic marker for human lung cancer. ? 2015 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84942885232&doi=10.1158%2f0008-5472.CAN-14-3265&partnerID=40&md5=3113aad67914adf731306a401c8248a9 https://scholars.lib.ntu.edu.tw/handle/123456789/516766 |
ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-14-3265 | SDG/關鍵字: | beta catenin; breast cancer resistance protein; caspase 3; CD133 antigen; protein Sox15; T cell factor 4 protein; transcription factor; transcription factor Twist1; unclassified drug; uvomorulin; beta catenin; cadherin; CD133 antigen; glycoprotein; leukocyte antigen; nuclear protein; peptide; protein binding; SOX15 protein, human; transcription factor Sox; transcription factor Twist; TWIST1 protein, human; ABCG2 gene; animal experiment; animal model; Article; autocrine effect; cancer recurrence; cancer stem cell; carcinogenicity; CASP3 gene; controlled study; epithelial mesenchymal transition; female; human; human tissue; in vitro study; in vivo study; lung cancer; mouse; nonhuman; paracrine signaling; phenotype; prediction; priority journal; promoter region; protein cleavage; protein protein interaction; transcription regulation; animal; cancer stem cell; DNA microarray; epithelial mesenchymal transition; gene expression profiling; gene expression regulation; genetics; HEK293 cell line; immunohistochemistry; lung tumor; metabolism; pathology; SCID mouse; tumor cell line; tumor recurrence; Western blotting; Wnt signaling pathway; xenograft; Animals; Antigens, CD; beta Catenin; Blotting, Western; Cadherins; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glycoproteins; HEK293 Cells; Humans; Immunohistochemistry; Lung Neoplasms; Mice, SCID; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Peptides; Protein Binding; SOX Transcription Factors; Transplantation, Heterologous; Twist Transcription Factor; Wnt Signaling Pathway |
顯示於: | 醫學系 |
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