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Sci Signal. 2014 Jun 10;7(329):ra56. doi: 10.1126/scisignal.2004870.

Memo is a copper-dependent redox protein with an essential role in migration and metastasis.

Author information

1
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
2
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan 20139, Italy. Molecular Medicine Program, Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy.
3
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. University of Basel, Basel 4002, Switzerland.
4
Novartis Institutes for BioMedical Research, Basel 4057, Switzerland.
5
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.
6
Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan 20141, Italy.
7
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141, Italy.
8
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.
9
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. University of Basel, Basel 4002, Switzerland. nancy.hynes@fmi.ch.

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.

PMID:
24917593
DOI:
10.1126/scisignal.2004870
[Indexed for MEDLINE]

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