Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2002-07-10Keywords
Antigens, SurfaceApoptosis
Breast Neoplasms
Cell Survival
Cytoplasm
Endothelial Growth Factors
Eukaryotic Initiation Factor-4E
*Gene Expression Regulation, Neoplastic
Humans
Integrin alpha6beta4IntegrinsLymphokinesOligonucleotides, AntisensePeptide Initiation FactorsPhosphorylationPolyribosomesProtein Structure, TertiaryProtein TransportRNA, BacterialRNA, MessengerReverse Transcriptase Polymerase Chain ReactionSignal TransductionTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsCancer BiologyNeoplasms
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Show full item recordAbstract
We define a novel mechanism by which integrins regulate growth factor expression and the survival of carcinoma cells. Specifically, we demonstrate that the alpha 6 beta 4 integrin enhances vascular endothelial growth factor (VEGF) translation in breast carcinoma cells. The mechanism involves the ability of this integrin to stimulate the phosphorylation and inactivation of 4E-binding protein (4E-BP1), a translational repressor that inhibits the function of eukaryotic translation initiation factor 4E (eIF-4E). The regulation of 4E-BP1 phosphorylation by alpha 6 beta 4 derives from the ability of this integrin to activate the PI-3K-Akt pathway and, consequently, the rapamycin-sensitive kinase mTOR that can phosphorylate 4E-BP1. Importantly, we show that this alpha 6 beta 4-dependent regulation of VEGF translation plays an important role in the survival of metastatic breast carcinoma cells by sustaining a VEGF autocrine signaling pathway that involves activation of PI-3K and Akt. These findings reveal that integrin-mediated activation of PI-3K-Akt is amplified by integrin-stimulated VEGF expression and they provide a mechanism that substantiates the reported role of alpha 6 beta 4 in carcinoma progression.Source
J Cell Biol. 2002 Jul 8;158(1):165-74. Epub 2002 Jul 8. Link to article on publisher's siteDOI
10.1083/jcb.200112015Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26280PubMed ID
12105188Related Resources
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