title: MicroRNA-584 and the protein phosphatase and actin regulator 1 (PHACTR1), a new signaling route through which transforming growth factor-β Mediates the migration and actin dynamics of breast cancer cells.
abstract: TGF-β plays an important role in breast cancer progression as a prometastatic factor, notably through enhancement of cell migration. It is becoming clear that microRNAs, a new class of small regulatory molecules, also play crucial roles in mediating tumor formation and progression. We found TGF-β to down-regulate the expression of the microRNA miR-584 in breast cancer cells. Furthermore, we identified PHACTR1, an actin-binding protein, to be positively regulated by TGF-β in a miR-584-dependent manner. Moreover, we found TGF-β-mediated down-regulation of miR-584 and increased expression of PHACTR1 to be required for TGF-β-induced cell migration of breast cancer cells. Indeed, both overexpression of miR-584 and knockdown of PHACTR1 resulted in a drastic reorganization of the actin cytoskeleton and reduced TGF-β-induced cell migration. Our data highlight a novel signaling route whereby TGF-β silences the expression of miR-584, resulting in enhanced PHACTR1 expression, and further leading to actin rearrangement and breast cancer cell migration.
authors.affiliation: Division of Medical Oncology, Department of Medicine, McGill University Health Center, Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Nadège
authors.initials: N
authors.lastname: Fils-Aimé
authors.forename: Meiou
authors.initials: M
authors.lastname: Dai
authors.forename: Jimin
authors.initials: J
authors.lastname: Guo
authors.forename: Mayada
authors.initials: M
authors.lastname: El-Mousawi
authors.forename: Bora
authors.initials: B
authors.lastname: Kahramangil
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Neel
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lebrun
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; C552781:MIRN584 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C570134:PHACTR1 protein, human; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta