scholarly journals The RNA-Binding Protein Musashi-1 Regulates Proteasome Subunit Expression in Breast Cancer- and Glioma-Initiating Cells

Stem Cells ◽  
2014 ◽  
Vol 32 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Chann Lagadec ◽  
Erina Vlashi ◽  
Patricia Frohnen ◽  
Yazeed Alhiyari ◽  
Mabel Chan ◽  
...  
2010 ◽  
Author(s):  
Ulus Atasoy ◽  
Matthew Gubin ◽  
Bob Calaluce ◽  
Wade Davis ◽  
Joseph Magee ◽  
...  

2008 ◽  
Vol 29 (11) ◽  
pp. 2053-2061 ◽  
Author(s):  
Álvaro D. Ortega ◽  
Sandra Sala ◽  
Enrique Espinosa ◽  
Manuel González-Barón ◽  
José M. Cuezva

2007 ◽  
Vol 28 (2) ◽  
pp. 772-783 ◽  
Author(s):  
Frank Vumbaca ◽  
Kathryn N. Phoenix ◽  
Daniel Rodriguez-Pinto ◽  
David K. Han ◽  
Kevin P. Claffey

ABSTRACT Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and facilitated translation. This study identified double-stranded RNA-binding protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF mRNA-binding protein which plays a key role in VEGF mRNA stability and protein synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3′ untranslated mRNA stability element. RNA interference targeting the DRBP76/NF90 isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA levels under hypoxic conditions and reduced mRNA stability. Transient overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein levels synthesized under normoxic and hypoxic conditions. Cells with stable repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic potential in an orthotopic breast tumor model. These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo.


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