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Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.

Research paper by Valentina V Evdokimova, Cristina C Tognon, Tony T Ng, Peter P Ruzanov, Natalya N Melnyk, Dieter D Fink, Alexey A Sorokin, Lev P LP Ovchinnikov, Elai E Davicioni, Timothy J TJ Triche, Poul H B PH Sorensen

Indexed on: 05 May '09Published on: 05 May '09Published in: Cancer Cell



Abstract

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.