title: p210bcr-abl induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1.
abstract: 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.
authors.affiliation: Institut de Physiologie et Biologie Cellulaires, Unité Mixte de Recherche Centre National de Recherche Scientifique (CNRS) 6187, Poitiers, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Rochelle
authors.forename: Thomas
authors.initials: T
authors.lastname: Daubon
authors.forename: Marleen
authors.initials: M
authors.lastname: Van Troys
authors.forename: Thomas
authors.initials: T
authors.lastname: Harnois
authors.forename: Davy
authors.initials: D
authors.lastname: Waterschoot
authors.forename: Christophe
authors.initials: C
authors.lastname: Ampe
authors.forename: Lydia
authors.initials: L
authors.lastname: Roy
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bourmeyster
authors.forename: Bruno
authors.initials: B
authors.lastname: Constantin
mesh_terms: D000656:Amoeba / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers; D051345:Destrin / Q000378:metabolism*; D016044:Fusion Proteins, bcr-abl / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D051345:Destrin; D009363:Neoplasm Proteins; C055533:adult T cell leukemia-derived factor; D016044:Fusion Proteins, bcr-abl; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein