An Sirna Screen Identifies RSK1 As a Key Modulator of Lung Cancer
Oncogene (2011) 30, 3513–3521 & 2011 Macmillan Publishers Limited All rights reserved 0950-9232/11 www.nature.com/onc ORIGINAL ARTICLE An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis R Lara1,7, FA Mauri2, H Taylor3, R Derua4, A Shia3, C Gray5, A Nicols5, RJ Shiner2, E Schofield6, PA Bates6, E Waelkens4, M Dallman3, J Lamb3, D Zicha5, J Downward7, MJ Seckl1 and OE Pardo1 1Department of Oncology, Hammersmith Campus, Cyclotron Building, London, UK; 2Histopathology Imperial College London, Hammersmith Campus, London, UK; 3Division of Cell and Molecular Biology, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, UK; 4Labo Proteı¨ne Fosforylatie en Proteomics, Katholieke Universiteit Leuven, Leuven, Belgium; 5Light Microscopy Department, London Research Institute, London, UK; 6Biomolecular Modelling Laboratory, London Research Institute, London, UK and 7Signal Transduction Laboratory, Cancer Research UK, London Research Institute, London, UK We performed a kinome-wide siRNA screen and identified Introduction 70 kinases altering cell migration in A549 lung cancer cells. In particular, ribosomal S6 kinase 1 (RSK1) Lung cancer is the most common cancer killer with silencing increased, whereas RSK2 and RSK4 down- a 5-year survival rate o5%. Non-small cell lung cancer regulation inhibited cell motility. In a secondary collagen- (NSCLC) accounts for 80% of cases of which adeno- based three-dimensional invasion screen, 38 of our hits carcinoma represents the majority. Most patients cross-validated, including RSK1 and RSK4. In two further present with metastatic lesions and are incurable. Hence, lung cancer cell lines, RSK1 but not RSK4 silencing a better understanding of the biological processes showed identical modulation of cell motility.
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