Translational Activation of Snail1 and Other Developmentally Regulated Transcription Factors by YB-1 Promotes an Epithelial-Mesenchymal Transition

Valentina Evdokimova, Cristina Tognon, Tony Ng, Peter Ruzanov, Natalya Melnyk, Dieter Fink, Alexey Sorokin, Lev P. Ovchinnikov, Elai Davicioni, Timothy J. Triche, Poul H.B. Sorensen

Research output: Contribution to journalArticlepeer-review

303 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)402-415
Number of pages14
JournalCancer Cell
Volume15
Issue number5
DOIs
StatePublished - May 5 2009
Externally publishedYes

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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