title: Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.
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.
authors.affiliation: Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan. msaeki@dent.osaka-u.ac.jp
authors.forename: Makio
authors.initials: M
authors.lastname: Saeki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egusa
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kamano
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kakihara
authors.forename: Walid A
authors.initials: WA
authors.lastname: Houry
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yatani
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamisaki
mesh_terms: D066258:Amphiregulin; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D019898:Autocrine Communication; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066255:EGF Family of Proteins; D055354:Exosomes / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019899:Paracrine Communication; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C509833:DNAAF10 protein, human; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C472351:RPAP3 protein, human