A Novel EGFR Extracellular Domain Mutant, EGFRΔ768, Possesses Distinct Biological and Biochemical Properties in Neuroblastoma.

Unlabelled: EGFR is a popular therapeutic target for many cancers. EGFR inhibitors have been tested in children with refractory neuroblastoma. Interestingly, partial response or stable disease was observed in a few neuroblastoma patients.

Perturbation of cytoskeleton dynamics by the opposing effects of Rac1 and Rac1b.

Rac1, a ubiquitously expressed member of the Rho GTPase family, plays a pivotal role in the regulation of multiple cellular processes including cytoskeleton reorganization, cell growth, differentiation and motility. Here we show that the tumor-specific splice variant of Rac1, Rac1b, negatively regulates Rac1 activity. The expression of Rac1b in HeLa cells interferes with Rac1 activation by PDGF, leads to a reduction in membrane-bound Rac1 and promotes an increase in Rho activity.

Deregulation of the cell cycle by breast tumor kinase (Brk).

Brk is a cytoplasmic nonreceptor tyrosine kinase that is overexpressed in breast tumors but undetectable in normal or benign mammary tissues. Brk promotes proliferation of human mammary epithelial cells and tumor growth in a mouse model, but the role of Brk in cell cycle regulation is not known. In this study, we describe the mechanism of Brk-induced deregulation of the cell cycle.

Redox-dependent downregulation of Rho by Rac.

Rac and Rho GTPases function as critical regulators of actin cytoskeleton remodelling during cell spreading and migration. Here we demonstrate that Rac-mediated reactive oxygen species (ROS) production results in the downregulation of Rho activity. The redox-dependent decrease in Rho activity is required for Rac-induced formation of membrane ruffles and integrin-mediated cell spreading.