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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amphiregulin
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Apoptosis Regulatory Proteins / metabolism*
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Autocrine Communication
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Carrier Proteins / genetics
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Cell Line, Tumor
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Cell Proliferation
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EGF Family of Proteins
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Exosomes / metabolism
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Female
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Glycoproteins / genetics*
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Glycoproteins / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins / genetics*
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Intercellular Signaling Peptides and Proteins / metabolism
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Neoplasm Invasiveness
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Paracrine Communication
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Protein Binding
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RNA Stability*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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AREG protein, human
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Amphiregulin
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Apoptosis Regulatory Proteins
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Carrier Proteins
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DNAAF10 protein, human
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EGF Family of Proteins
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Glycoproteins
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Intercellular Signaling Peptides and Proteins
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RNA, Messenger
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RPAP3 protein, human
Grants and funding
This work was supported by the Japan Society for the Promotion of Science (C24592795). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.