p210bcr-abl induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1

被引：15

作者：

Rochelle, Tristan ^{[1
]}

Daubon, Thomas ^{[1
]}

Van Troys, Marleen ^{[3
,4
]}

Harnois, Thomas ^{[2
,5
]}

Waterschoot, Davy ^{[3
,4
]}

Ampe, Christophe ^{[3
,4
]}

Roy, Lydia ^{[1
,5
,6
]}

Bourmeyster, Nicolas ^{[1
,2
,5
]}

Constantin, Bruno ^{[1
]}

机构：

[1] Univ Poitiers, CNRS, UMR 6187, Inst Physiol & Biol Cellulaires, F-86022 Poitiers, France

[2] Univ Poitiers, Plateforme Prote ProteomeUP, F-86022 Poitiers, France

[3] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium

[4] Univ Ghent VIB, Dept Med Prot Res, B-9052 Ghent, Belgium

[5] Ctr Hosp Univ Poitiers, Poitiers, France

[6] INSERM, CIC 802, Poitiers, France

来源：

FASEB JOURNAL | 2013年 / 27卷 / 01期

关键词：

isoform selectivity; cell migration; GTPases; actin-binding proteins; signalplex; leukemia; TUMOR-CELL INVASION; ACTIN-DEPOLYMERIZING FACTOR; BCR-ABL ONCOGENE; CHEMOTACTIC RESPONSE; RHO-GTPASES; LIM-KINASE; MIGRATION; COFILIN; BCR/ABL; PHOSPHORYLATION;

D O I：

10.1096/fj.12-205112

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We previously demonstrated that the BcrAbl 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.-Rochelle, T., Daubon, T., Van Troys, M., Harnois, T., Waterschoot, D., Ampe, C., Roy, L., Bourmeyster, N., Constantin, B. p210(bcr-abl) induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1. FASEB J. 27, 123-134 (2013). www.fasebj.org

引用

页码：123 / 134

页数：12