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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Stöhr, Nadine Köhn, Marcel Lederer, Marcell Glass, Markus Reinke, Claudia Singer, Robert H. Hüttelmaier, Stefan |
| Description | Country affiliation: Germany Author Affiliation: Stöhr N ( Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University of Halle, Halle, Germany.) |
| Abstract | In primary neurons, the oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA-binding protein 1) controls spatially restricted ß-actin (ACTB) mRNA translation and modulates growth cone guidance. In cultured tumor-derived cells, IGF2BP1 was shown to regulate the formation of lamellipodia and invadopodia. However, how and via which target mRNAs IGF2BP1 controls the motility of tumor-derived cells has remained elusive. In this study, we reveal that IGF2BP1 promotes the velocity and directionality of tumor-derived cell migration by determining the cytoplasmic fate of two novel target mRNAs: MAPK4 and PTEN. Inhibition of MAPK4 mRNA translation by IGF2BP1 antagonizes MK5 activation and prevents phosphorylation of HSP27, which sequesters actin monomers available for F-actin polymerization. Consequently, HSP27-ACTB association is reduced, mobilizing cellular G-actin for polymerization in order to promote the velocity of cell migration. At the same time, stabilization of the PTEN mRNA by IGF2BP1 enhances PTEN expression and antagonizes PIP(3)-directed signaling. This enforces the directionality of cell migration in a RAC1-dependent manner by preventing additional lamellipodia from forming and sustaining cell polarization intrinsically. IGF2BP1 thus promotes the velocity and persistence of tumor cell migration by controlling the expression of signaling proteins. This fine-tunes and connects intracellular signaling networks in order to enhance actin dynamics and cell polarization. |
| File Format | HTM / HTML |
| ISSN | 08909369 |
| e-ISSN | 15495477 |
| DOI | 10.1101/gad.177642.111 |
| Journal | Genes & Development |
| Issue Number | 2 |
| Volume Number | 26 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2012-01-15 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Intracellular Signaling Peptides And Proteins Metabolism Pten Phosphohydrolase Protein-serine-threonine Kinases Signal Transduction Actins Cell Line, Tumor Cell Movement Cell Polarity Physiology Enzyme Activation Extracellular Signal-regulated Map Kinases Hsp27 Heat-shock Proteins Phosphorylation Rna, Messenger Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Developmental Biology |
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