Evdokimova Valentina, Tognon Cristina, Ng Tony, Ruzanov Peter, Melnyk Natalya, Fink Dieter, Sorokin Alexey, Ovchinnikov Lev P, Davicioni Elai, Triche Timothy J, Sorensen Poul H B
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
Cancer Cell. 2009 May 5;15(5):402-15. doi: 10.1016/j.ccr.2009.03.017.
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.
转录/翻译调节蛋白Y盒结合蛋白1（YB-1）表达的增加与癌症侵袭性相关，尤其是在乳腺癌中。在此我们证实，侵袭性乳腺癌细胞中YB-1水平升高，且与E-钙黏蛋白表达降低及患者预后不良相关。在非侵袭性乳腺上皮细胞中强制表达YB-1可诱导上皮-间质转化（EMT），同时伴有转移潜能增强和增殖率降低。YB-1直接激活编码Snail1和其他转录因子的信使核糖核酸的非帽依赖性翻译，这些转录因子与上皮和生长相关基因的下调以及间质基因的激活有关。因此，YB-1的翻译调控是一个限制点，可实现诱导EMT的转录因子网络的协同表达，这些转录因子可能共同作用促进转移扩散。
