title: Muscleblind-like 1 suppresses breast cancer metastatic colonization and stabilizes metastasis suppressor transcripts.
abstract: Post-transcriptional deregulation is a defining feature of metastatic cancer. While many microRNAs have been implicated as regulators of metastatic progression, less is known about the roles and mechanisms of RNA-binding proteins in this process. We identified muscleblind-like 1 (MBNL1), a gene implicated in myotonic dystrophy, as a robust suppressor of multiorgan breast cancer metastasis. MBNL1 binds the 3' untranslated regions (UTRs) of DBNL (drebrin-like protein) and TACC1 (transforming acidic coiled-coil containing protein 1)-two genes that we implicate as metastasis suppressors. By enhancing the stability of these genes' transcripts, MBNL1 suppresses cell invasiveness. Consistent with these findings, elevated MBNL1 expression in human breast tumors is associated with reduced metastatic relapse likelihood. Our findings delineate a post-transcriptional network that governs breast cancer metastasis through RNA-binding protein-mediated transcript stabilization.
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fish
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Pencheva
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Hani
authors.initials: H
authors.lastname: Goodarzi
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Hien
authors.initials: H
authors.lastname: Tran
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Sohail F
authors.initials: SF
authors.lastname: Tavazoie
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000503:physiopathology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D011485:Protein Binding; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C493663:MBNL1 protein, human; C479922:Mbnl1 protein, mouse; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D016601:RNA-Binding Proteins
keywords: MBNL1; RNA-binding proteins; metastasis