Role of β-arrestin 1 in the metastatic progression of colorectal cancer

F. Gregory Buchanan, D. Lee Gorden, Pranathi Matta, Qiong Shi, Lynn M. Matrisian, Raymond N. DuBois

Research output: Contribution to journalArticle

205 Scopus citations

Abstract

G protein-coupled receptor ligand-dependent transactivation of growth factor receptors has been implicated in human cancer cell proliferation, migration, and cell survival. For example, prostaglandin E2 (PGE 2)-induced transactivation of the EGF receptor (EGFR) in colorectal carcinoma cells is mediated by means of a c-Src-dependent mechanism and regulates cell proliferation and migration. Recent evidence indicates that β-arrestin 1 may act as an important mediator in G protein-coupled receptor-induced activation of c-Src. Whether β-arrestin 1 serves a functional role in these events is, however, unknown. We investigated the effects of PGE2 on colorectal cancer cells expressing WT and mutant β-arrestin 1. Here we report that PGE2 induces the association of a prostaglandin E receptor 4/β-arrestin 1/c-Src signaling complex resulting in the transactivation of the EGFR and downstream Akt (PKB) signaling. The interaction of β-arrestin 1 and c-Src is critical for the regulation of colorectal carcinoma cell migration in vitro as well as metasiatic spread of disease to the liver in vivo. These results show that the prostaglandin E/β-arrestin 1/c-Src signaling complex is a crucial step in PGE 2-mediated transactivation of the EGFR and may play a pivotal role in tumor metastasis. Furthermore, our data implicate a functional role for β-arrestin 1 as a mediator of cellular migration and metastasis.

Original languageEnglish (US)
Pages (from-to)1492-1497
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number5
DOIs
StatePublished - Jan 31 2006

Keywords

  • EGF receptor
  • Metastasis
  • Prostaglandin E
  • Prostaglandin E receptor
  • c-Src

ASJC Scopus subject areas

  • General

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