Exosome-Bound WD Repeat Protein Monad Inhibits Breast Cancer Cell Invasion by Degrading Amphiregulin mRNAReport as inadecuate




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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.



Author: Makio Saeki , Hiroshi Egusa, Yuya Kamano, Yoshito Kakihara, Walid A. Houry, Hirofumi Yatani, Shinzaburo Noguchi, Yoshinori Kamisa

Source: http://plos.srce.hr/



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