IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling

Nadine Stöhr, Marcel Köhn, Marcell Lederer, Markus Glaß, Claudia Reinke, Robert H. Singer, Stefan Höttelmaier

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

In primary neurons, the oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA-binding protein 1) controls spatially restricted b-actin (ACTB) mRNA translation and modulates growth cone guidance. In cultured tumorderived 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 PIP3-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.

Original languageEnglish (US)
Pages (from-to)176-189
Number of pages14
JournalGenes and Development
Volume26
Issue number2
DOIs
StatePublished - Jan 15 2012

Fingerprint

Cell Movement
Carrier Proteins
Messenger RNA
Actins
Pseudopodia
Protein Biosynthesis
Polymerization
Neoplasms
Growth Cones
RNA-Binding Proteins
Cultured Cells
Phosphorylation
Neurons

Keywords

  • Cell migration
  • HSP27
  • IGF2BP1
  • MAPK4
  • PTEN
  • ZBP1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Stöhr, N., Köhn, M., Lederer, M., Glaß, M., Reinke, C., Singer, R. H., & Höttelmaier, S. (2012). IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes and Development, 26(2), 176-189. https://doi.org/10.1101/gad.177642.111

IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. / Stöhr, Nadine; Köhn, Marcel; Lederer, Marcell; Glaß, Markus; Reinke, Claudia; Singer, Robert H.; Höttelmaier, Stefan.

In: Genes and Development, Vol. 26, No. 2, 15.01.2012, p. 176-189.

Research output: Contribution to journalArticle

Stöhr, N, Köhn, M, Lederer, M, Glaß, M, Reinke, C, Singer, RH & Höttelmaier, S 2012, 'IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling', Genes and Development, vol. 26, no. 2, pp. 176-189. https://doi.org/10.1101/gad.177642.111
Stöhr, Nadine ; Köhn, Marcel ; Lederer, Marcell ; Glaß, Markus ; Reinke, Claudia ; Singer, Robert H. ; Höttelmaier, Stefan. / IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. In: Genes and Development. 2012 ; Vol. 26, No. 2. pp. 176-189.
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