Translational Activation of Snail1 and Other Developmentally Regulated Transcription Factors by YB-1 Promotes an Epithelial-Mesenchymal Transition
Translational Activation of Snail1 and Other Developmentally Regulated Transcription Factors by YB-1 Promotes an Epithelial-Mesenchymal Transition
复制标题
DOI：
10.1016/j.ccr.2009.03.017
复制
发表时间：
2009-05-05
期刊：
影响因子：
50.3
通讯作者：
Sorensen, Poul H. B.
中科院分区：
文献类型：
--
作者：
Evdokimova, Valentina;Tognon, Cristina;Sorensen, Poul H. B.
转录/翻译调节蛋白Y-box结合蛋白-1(YB-1)的表达增加与肿瘤的侵袭性有关，尤其是在乳腺癌中。在这里，我们确定YB-1水平在浸润性乳腺癌细胞中升高，并与E-钙粘附素表达减少和患者生存不良相关。YB-1在非侵袭性乳腺上皮细胞中的增强表达诱导了上皮-间充质转化(EMT)，并伴随着转移潜能的增强和增殖率的降低。YB-1直接激活编码Snail1和其他转录因子的信使RNA的帽子非依赖性翻译，这些转录因子与上皮和生长相关基因的下调以及间充质基因的激活有关。因此，YB-1的翻译调控是一个限制点，使EMT诱导的转录因子网络能够协调表达，可能共同作用促进转移扩散。
Increased expression of the transcription/translation regulatory protein Y-box binding protein-1 (YB-1) is associated with cancer aggressiveness, particularly in breast carcinoma. Here we establish that YB-1 levels are elevated in invasive breast cancer cells and correlate with reduced expression of E-cadherin and poor patient survival. Enforced expression of YB-1 in noninvasive breast epithelial cells induced an epithelial-mesenchymal transition (EMT) accompanied by enhanced metastatic potential and reduced proliferation rates. YB-1 directly activates cap-independent translation of messenger RNAs encoding Snail1 and other transcription factors implicated in downregulation of epithelial and growth-related genes and activation of mesenchymal genes. Hence, translational regulation by YB-1 is a restriction point enabling coordinated expression of a network of EMT-inducing transcription factors, likely acting together to promote metastatic spread.