Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.
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.
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada. v.evdokimova@gmail.com
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
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1
D015820:Cadherins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012315:RNA Caps; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human