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

V Evdokimova, C Tognon, T Ng, P Ruzanov, N Melnyk… - Cancer cell, 2009 - cell.com
V Evdokimova, C Tognon, T Ng, P Ruzanov, N Melnyk, D Fink, A Sorokin, LP Ovchinnikov
Cancer cell, 2009cell.com
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 …
Summary
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.
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