Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination. - Archive ouverte HAL Access content directly
Journal Articles Blood Cancer Journal Year : 2011

Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination.

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Abstract

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.

Dates and versions

inserm-00726858 , version 1 (31-08-2012)

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A. Colomba, Sylvie Giuriato, Emilie Dejean, K. Thornber, Georges Delsol, et al.. Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination.. Blood Cancer Journal, 2011, 1 (6), pp.e21. ⟨10.1038/bcj.2011.19⟩. ⟨inserm-00726858⟩
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