The Nucleophosmin-Anaplastic Lymphoma Kinase Oncogene Interacts, Activates, and Uses the Kinase PIKfyve to Increase Invasiveness

• DOI: 10.1074/jbc.m111.227512
• Publication Date: 2011-07-08T13:43:01Z
• Authors: Sophie Dupuis-Cor...; Frédéric Lagarrigue; Damien Ramel; Gaëtan Chicanne; Estelle Saland; Frédérique Gaits-...; Bernard Payrastre; Hélène Tronchère
• Keywords: Nucleophosmin

NPM-ALK is a chimeric tyrosine kinase detected in most anaplastic large cell lymphomas that results from the reciprocal translocation t(2,5)(p23;q35) fuses N-terminal domain of nucleophosmin (NPM) to catalytic lymphoma (ALK) receptor. The constitutive activity responsible for its oncogenicity through stimulation several downstream signaling pathways, leading proliferation, migration, and survival. We demonstrated previously high level phosphatidylinositol 5-phosphate measured NPM-ALK-expressing cells controlled by phosphoinositide PIKfyve, lipid known role vesicular trafficking. Here, we show PIKfyve associates with interaction involves 181–300 region oncogene. Moreover, demonstrate oncogene controls but dispensable formation complex. Silencing or inhibition using siRNA inhibitor YM201636 have no effect on NPM-ALK-mediated proliferation migration strongly reduce invasive capacities their capacity degrade extracellular matrix. Accordingly, immunofluorescence studies confirm perturbation matrix metalloproteinase 9 localization at surface defect maturation. Altogether, these suggest invasion.