Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation.
Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation.
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DOI：
10.1158/0008-5472.can-13-2466
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发表时间：
2014-02-01
期刊：
影响因子：
11.2
通讯作者：
Pestell RG
中科院分区：
文献类型：
--
作者：
Wu K;Chen K;Wang C;Jiao X;Wang L;Zhou J;Wang J;Li Z;Addya S;Sorensen PH;Lisanti MP;Quong A;Ertel A;Pestell RG
上皮-间质转化（epithelial-mesenchymal transition， EMT）通过转录和翻译机制增强细胞侵袭性，赋予肿瘤细胞类似癌症干细胞的特征。维持EMT转录和翻译抑制和细胞侵袭的机制尚不清楚。本研究中，细胞命运决定因子Dachshund （DACH1）通过灭活Y盒结合蛋白（YB-1）抑制蜗牛细胞质翻译诱导，从而抑制EMT。在细胞核中，DACH1可拮抗yb -1介导的调控细胞侵袭的致癌转录模块。DACH1阻断yb -1诱导的小鼠乳腺肿瘤生长和EMT。在基底样乳腺癌（BLBC）中，DACH1的表达降低和YB-1的表达升高与无转移生存率低相关。DACH1抑制EMT和肿瘤侵袭的细胞质翻译和核转录事件的缺失可能导致基底样乳腺癌（一种相对侵袭性的疾病亚型）预后不良。
The epithelial-mesenchymal transition (EMT) enhances cellular invasiveness and confers tumor cells with cancer stem cell like characteristics, through transcriptional and translational mechanisms. The mechanisms maintaining transcriptional and translational repression of EMT and cellular invasion are poorly understood. Herein, the cell fate-determination factor Dachshund (DACH1), suppressed EMT via repression of cytoplasmic translational induction of Snail by inactivating the Y box-binding protein (YB-1). In the nucleus, DACH1 antagonized YB-1-mediated oncogenic transcriptional modules governing cell invasion. DACH1 blocked YB-1-induced mammary tumor growth and EMT in mice. In basal-like breast cancer (BLBC) the reduced expression of DACH1 and increased YB-1, correlated with poor metastasis free survival. The loss of DACH1 suppression of both cytoplasmic translational and nuclear transcriptional events governing EMT and tumor invasion may contribute to poor prognosis in basal-like forms of breast cancer, a relatively aggressive disease subtype.