Journal
BLOOD CANCER JOURNAL
Volume 1, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bcj.2011.19
Keywords
anaplastic lymphomas; NPM-ALK; dissemination; Rac1 GTPase
Categories
Funding
- INSERM
- Ministere de la Recherche et de la Technologie
- ARC
- INCa
- La Ligue contre le Cancer
- Canceropole GSO
- Pole de competitivite Cancer-Biosante/Fonds uniques interministeriels des poles de competitivite
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Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM-ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM-ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM-ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas. Blood Cancer Journal (2011) 1, e21; doi: 10.1038/bcj.2011.19; published online 3 June 2011
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