Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.
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.
Mesh Terms:
Apoptosis Regulatory Proteins, Autocrine Communication, Breast Neoplasms, Carrier Proteins, Cell Line, Tumor, Cell Proliferation, Exosomes, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glycoproteins, Humans, Intercellular Signaling Peptides and Proteins, Neoplasm Invasiveness, Paracrine Communication, Protein Binding, RNA Stability, RNA, Messenger
Apoptosis Regulatory Proteins, Autocrine Communication, Breast Neoplasms, Carrier Proteins, Cell Line, Tumor, Cell Proliferation, Exosomes, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glycoproteins, Humans, Intercellular Signaling Peptides and Proteins, Neoplasm Invasiveness, Paracrine Communication, Protein Binding, RNA Stability, RNA, Messenger
PLoS ONE
Date: Jul. 12, 2013
PubMed ID: 23844004
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