Memo Is a Copper-Dependent Redox Protein with an Essential Role in Migration and Metastasis

作者：MacDonald Gwen; Nalvarte Ivan; Smirnova Tatiana; Vecchi Manuela; Aceto Nicola; Dolemeyer Arno; Frei Anna; Lienhard Susanne; Wyckoff Jeffrey; Hess Daniel; Seebacher Jan; Keusch Jeremy J; Gut Heinz; Salaun Daniele; Mazzarol Giovanni; Disalvatore Davide; Bentires Alj Mohamed; Di Fiore Pier Paolo; Badache Ali; Hynes Nancy E^*

来源：Science Signaling, 2014, 7(329): ra56.

DOI：10.1126/scisignal.2004870

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 O-2(-) by NADPH ( reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 1 ( NOX1) in breast cancer cells. Memo abundance was increased in %26gt; 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.

• 出版日期2014-6-10