title: Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination.
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.
authors: A
authors: A
authors: Colomba
authors: S
authors: S
authors: Giuriato
authors: E
authors: E
authors: Dejean
authors: K
authors: K
authors: Thornber
authors: G
authors: G
authors: Delsol
authors: H
authors: H
authors: Tronchère
authors: F
authors: F
authors: Meggetto
authors: B
authors: B
authors: Payrastre
authors: F
authors: F
authors: Gaits-Iacovoni