Integrin (α6β4) regulation of eIF-4E activity and VEGF translation
| Autor: | Arthur M. Mercurio, Robin E. Bachelder, Leslie M. Shaw, Jun Chung, Elizabeth A. Lipscomb |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cytoplasm Integrins Cell Survival Integrin Apoptosis Breast Neoplasms Endothelial Growth Factors Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Peptide Initiation Factors Tumor Cells Cultured Humans RNA Messenger Phosphorylation Autocrine signalling PI3K/AKT/mTOR pathway 030304 developmental biology integrin VEGF translation carcinoma eIF-4E Integrin alpha6beta4 0303 health sciences Lymphokines Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factors EIF4E Cell Biology Oligonucleotides Antisense 3. Good health Cell biology Protein Structure Tertiary Vascular endothelial growth factor Gene Expression Regulation Neoplastic Vascular endothelial growth factor A Protein Transport RNA Bacterial Eukaryotic Initiation Factor-4E chemistry 030220 oncology & carcinogenesis Polyribosomes Antigens Surface Cancer research biology.protein Integrin beta 6 Signal transduction Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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