Memoは銅依存性レドックスタンパク質であり、移動と転移に必須の役割を持つ

Sci. Signal., 10 June 2014
Vol. 7, Issue 329, p. ra56
[DOI: 10.1126/scisignal.2004870]

Gwen MacDonald^1*, Ivan Nalvarte^1*†, Tatiana Smirnova¹, Manuela Vecchi^2,3, Nicola Aceto^1,4‡, Arno Dolemeyer⁵, Anna Frei^1,4, Susanne Lienhard¹, Jeffrey Wyckoff^1§, Daniel Hess¹, Jan Seebacher¹, Jeremy J. Keusch¹, Heinz Gut¹, Daniele Salaun⁶, Giovanni Mazzarol⁷, Davide Disalvatore⁸, Mohamed Bentires-Alj¹, Pier Paolo Di Fiore^2,3,9, Ali Badache⁶, and Nancy E. Hynes^1,4‖

¹ Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
² IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan 20139, Italy.
³ Molecular Medicine Program, Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy.
⁴ University of Basel, Basel 4002, Switzerland.
⁵ Novartis Institutes for BioMedical Research, Basel 4057, Switzerland.
⁶ 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.
⁷ Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan 20141, Italy.
⁸ Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141, Italy.
⁹ Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan 20122, Italy.

^* These authors contributed equally to this work.

† Present address: Department of Biosciences and Nutrition, Karolinska Institute, 14183 Huddinge, Sweden.

‡ Present address: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA.

§ Present address: Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02138, USA.

‖ Corresponding author. E-mail: nancy.hynes@fmi.ch

要約

Memoは進化的に保存されたタンパク質であり、細胞の運動性に重要な役割を有する。われわれは、Memoがin vitroでの乳がん細胞の遊走と浸潤、in vivoでの乳がん細胞異種移植片からの自発性の肺転移に必要であることを見出した。生化学アッセイから、Memoが銅依存性酸化還元酵素であり、より酸化的な細胞内環境を促進し、遊走に関与する細胞構造において活性酸素種（ROS）の産生を刺激することが明らかになった。Memoは、NADPH（還元型ニコチンアミドアデニンジヌクレオチドリン酸）オキシダーゼ1（NOX1）によるROS O_{2-の持続的な産生にも必要であった。Memoの存在量は、調べた原発性乳房腫瘍の40％超で増加しており、高侵襲性疾患の臨床パラメーターと相関し、早期遠隔転移の独立した予後因子であった。}

G. MacDonald, I. Nalvarte, T. Smirnova, M. Vecchi, N. Aceto, A. Dolemeyer, A. Frei, S. Lienhard, J. Wyckoff, D. Hess, J. Seebacher, J. J. Keusch, H. Gut, D. Salaun, G. Mazzarol, D. Disalvatore, M. Bentires-Alj, P. P. Di Fiore, A. Badache, N. E. Hynes, Memo Is a Copper-Dependent Redox Protein with an Essential Role in Migration and Metastasis. Sci. Signal. 7, ra56 (2014).