RT Journal Article
SR Electronic
T1 Memo Is a Copper-Dependent Redox Protein with an Essential Role in Migration and Metastasis
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra56
OP ra56
DO 10.1126/scisignal.2004870
VO 7
IS 329
A1 MacDonald, Gwen
A1 Nalvarte, Ivan
A1 Smirnova, Tatiana
A1 Vecchi, Manuela
A1 Aceto, Nicola
A1 Doelemeyer, Arno
A1 Frei, Anna
A1 Lienhard, Susanne
A1 Wyckoff, Jeffrey
A1 Hess, Daniel
A1 Seebacher, Jan
A1 Keusch, Jeremy J.
A1 Gut, Heinz
A1 Salaun, Daniele
A1 Mazzarol, Giovanni
A1 Disalvatore, Davide
A1 Bentires-Alj, Mohamed
A1 Di Fiore, Pier Paolo
A1 Badache, Ali
A1 Hynes, Nancy E.
YR 2014
UL http://stke.sciencemag.org/content/7/329/ra56.abstract
AB 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.