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Article Dans Une Revue FASEB Journal Année : 2013

p210 bcr-abl induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1

Résumé

We previously demonstrated that the Bcr-Abl oncogene, p210(bcr-abl), through its unique GEF domain, specifically activates RhoA and induces spontaneous amoeboid motility. We intend to study the pathways downstream RhoA controlling amoeboid motility. Mouse prolymphoblastic cells (Ba/F3 cell line) expressing different forms of Bcr-Abl were embedded in 3-dimensional (3D) Matrigel to study motility and explore the effects of inhibiting Rho pathway (inhibitors and siRNAs). The phosphorylation levels of cofilin-1 and destrin were analyzed by 2-dimensional electrophoresis. Composition of Bcr-Abl signalplex in different conditions was determined by coimmunoprecipitation. Ba/F3p190 and Ba/F3 expressing a mutant form of p210(bcr-abl) (unable to activate RhoA) cells presented a spontaneous motility, but not an amoeboid type. p210(bcr-abl)-induced amoeboid motility in a 3D matrix requires isoform-specific RhoA/ROCK-1/destrin signaling. Next to the conventional Rho/ROCK/MLC/myosin pathway, this pathway is a crucial determinant for amoeboid motility, specific for the destrin isoform (and not its coexpressed homologue cofilin-1). Also, the presence of destrin (and not cofilin-1) in the p210(bcr-abl) complex is dependent on ROCK1, and this signalplex is required for amoeboid motility. This underscores isoform-specific function within the ADF/cofilin family and provides new insight into Bcr-Abl signaling to amoeboid motility and possible impact on understanding chronic myeloid leukemia progression.
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Dates et versions

hal-01705238 , version 1 (17-11-2022)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Citer

Tristan Rochelle, Thomas Daubon, Marleen van Troys, Thomas Harnois, Davy Waterschoot, et al.. p210 bcr-abl induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1. FASEB Journal, 2013, 27 (1), pp.123-134. ⟨10.1096/fj.12-205112⟩. ⟨hal-01705238⟩
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