https://scholars.lib.ntu.edu.tw/handle/123456789/462223
標題: | Epithelial-mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1 | 作者: | Li C.-W. Xia W. Huo L. Lim S.-O. Wu Y. Hsu J.L. Chao C.-H. Yamaguchi H. Yang N.-K. Ding Q. Wang Y. Lai Y.-J. LaBaff A.M. Wu T.-J. BEEN-REN LIN Yang M.-H. Hortobagyi G.N. Hung M.-C. |
公開日期: | 2012 | 卷: | 72 | 期: | 5 | 起(迄)頁: | 1290-1300 | 來源出版物: | Cancer Research | 摘要: | Proinflammatory cytokines produced in the tumor microenvironment facilitate tumor development and metastatic progression. In particular, TNF-α promotes cancer invasion and angiogenesis associated with epithelial-mesenchymal transition (EMT); however, the mechanisms underlying its induction of EMT in cancer cells remain unclear. Here we show that EMT and cancer stemness properties induced by chronic treatment with TNF-α are mediated by the upregulation of the transcriptional repressor Twist1. Exposure to TNF-α rapidly induced Twist1 mRNA and protein expression in normal breast epithelial and breast cancer cells. Both IKK-β and NF-κB p65 were required for TNF-α-induced expression of Twist1, suggesting the involvement of canonical NF-κB signaling. In support of this likelihood, we defined a functional NF-κB-binding site in the Twist1 promoter, and overexpression of p65 was sufficient to induce transcriptional upregulation of Twist1 along with EMT in mammary epithelial cells. Conversely, suppressing Twist1 expression abrogated p65-induced cell migration, invasion, EMT, and stemness properties, establishing that Twist1 is required for NF-κB to induce these aggressive phenotypes in breast cancer cells. Taken together, our results establish a signaling axis through which the tumor microenvironment elicits Twist1 expression to promote cancer metastasis. We suggest that targeting NF-κB-mediated Twist1 upregulation may offer an effective a therapeutic strategy for breast cancer treatment. ?2012 AACR. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84863280130&doi=10.1158%2f0008-5472.CAN-11-3123&partnerID=40&md5=2f22d8ef9f0c4a6362068ac6157287fc https://scholars.lib.ntu.edu.tw/handle/123456789/462223 |
ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-11-3123 | SDG/關鍵字: | I kappa B kinase beta; immunoglobulin enhancer binding protein; messenger RNA; transcription factor RelA; transcription factor Twist; transcription factor Twist1; tumor necrosis factor alpha; unclassified drug; animal cell; animal experiment; animal model; animal tissue; article; binding affinity; binding site; cell invasion; cell migration; controlled study; embryo; epithelial mesenchymal transition; gene; gene expression; human; human tissue; mouse; nonhuman; priority journal; promoter region; protein binding; protein expression; protein function; signal transduction; transcription regulation; tumor microenvironment; TWIST1 gene; Animals; Breast Neoplasms; Carrier Proteins; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Female; Humans; I-kappa B Kinase; Inflammation; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Proteins; NF-kappa B; Nuclear Proteins; Transcriptional Activation; Transfection; Tumor Necrosis Factor-alpha; Twist Transcription Factor; Up-Regulation |
顯示於: | 醫學系 |
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