The N-terminal domain of G3BP enhances cell motility and invasion by posttranscriptional regulation of BART

Keisuke Taniuchi, Isao Nishimori, Michael A Hollingsworth

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The regulation of mRNA stability plays an important role in the control of gene expression during cell motility and invasion. We previously reported that GTPase-activating protein [Src homology 3 (SH3) domain] binding protein (G3BP), a marker of cytoplasmic stress granules that are formed in stressed cells and regulate mRNA stability, binds and degrades the mRNA of binder of Arl two (BART) that inhibits retroperitoneal invasion and hepatic metastasis of pancreatic cancer cells. Here, we report that overexpression of the amino (N)-terminal region of G3BP, including the binding region for BART mRNA, dominant-negatively inhibits formation of the complex between endogenous G3BP and BART mRNA, and increases the expression of BART. This, in turn, inhibits the invasiveness of pancreatic cancer cells. On the other hand, the carboxy (C)-terminal region of G3BP is associated with phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) that initiates stress granule assembly but does not modulate the posttranscriptional regulation of BART mRNA. N-terminal G3BP also plays a role in regulating secreted matrix metalloproteinases, transcription factors, and a variety of genes involved in cell adhesion and motility. These results suggest that N-terminal G3BP contributes to posttranscriptional regulation of cell motility and invasive capacity of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)856-866
Number of pages11
JournalMolecular Cancer Research
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2011

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Cell Movement
Pancreatic Neoplasms
Messenger RNA
RNA Stability
Secreted Matrix Metalloproteinases
Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Cytoplasmic Granules
GTPase-Activating Proteins
src Homology Domains
Cell Adhesion
Carrier Proteins
Transcription Factors
Phosphorylation
Neoplasm Metastasis
Gene Expression
Liver
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

The N-terminal domain of G3BP enhances cell motility and invasion by posttranscriptional regulation of BART. / Taniuchi, Keisuke; Nishimori, Isao; Hollingsworth, Michael A.

In: Molecular Cancer Research, Vol. 9, No. 7, 01.07.2011, p. 856-866.

Research output: Contribution to journalArticle

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