title: Memo is a copper-dependent redox protein with an essential role in migration and metastasis.
abstract: Memo is an evolutionarily conserved protein with a critical role in cell motility. We found that Memo was required for migration and invasion of breast cancer cells in vitro and spontaneous lung metastasis from breast cancer cell xenografts in vivo. Biochemical assays revealed that Memo is a copper-dependent redox enzyme that promoted a more oxidized intracellular milieu and stimulated the production of reactive oxygen species (ROS) in cellular structures involved in migration. Memo was also required for the sustained production of the ROS O2- by NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 1 (NOX1) in breast cancer cells. Memo abundance was increased in >40% of the primary breast tumors tested, was correlated with clinical parameters of aggressive disease, and was an independent prognostic factor of early distant metastasis.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Gwen
authors.initials: G
authors.lastname: MacDonald
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nalvarte
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Smirnova
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan 20139, Italy. Molecular Medicine Program, Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vecchi
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. University of Basel, Basel 4002, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Aceto
authors.affiliation: Novartis Institutes for BioMedical Research, Basel 4057, Switzerland.
authors.forename: Arno
authors.initials: A
authors.lastname: Dolemeyer
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. University of Basel, Basel 4002, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Frei
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lienhard
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wyckoff
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hess
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Seebacher
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Keusch
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gut
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm (U1068), Institut Paoli-Calmettes, Aix-Marseille Université, Centre National de la Recherche Scientifique (UMR7258), Marseille 13009, France.
authors.forename: Daniele
authors.initials: D
authors.lastname: Salaun
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mazzarol
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Disalvatore
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bentires-Alj
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan 20139, Italy. Molecular Medicine Program, Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy. Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan 20122, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm (U1068), Institut Paoli-Calmettes, Aix-Marseille Université, Centre National de la Recherche Scientifique (UMR7258), Marseille 13009, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Badache
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. University of Basel, Basel 4002, Switzerland. nancy.hynes@fmi.ch.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Hynes
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D003300:Copper / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009249:NADP / Q000235:genetics / Q000378:metabolism; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D019159:Nonheme Iron Proteins / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C527585:MEMO1 protein, human; D009363:Neoplasm Proteins; D019159:Nonheme Iron Proteins; D013481:Superoxides; D009249:NADP; D003300:Copper; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human