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PLoS One. 2013 Jul 3;8(7):e67326. doi: 10.1371/journal.pone.0067326. Print 2013.

Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.

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1
Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan. msaeki@dent.osaka-u.ac.jp

Abstract

Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

PMID:
23844004
PMCID:
PMC3701000
DOI:
10.1371/journal.pone.0067326
[Indexed for MEDLINE]
Free PMC Article
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