P-Rex1 is dispensable for Erk activation and mitogenesis in breast cancer.

P-Rex1 is dispensable for Erk activation and mitogenesis in breast cancer. Oncotarget. 2018 Jun 19;9(47):28612-28624 Authors: Barrio-Real L, Lopez-Haber C, Casado-Medrano V, Goglia AG, Toettcher JE, Caloca MJ, Kazanietz MG Abstract Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1 (P-Rex1) is a key mediator of growth factor-induced activation of Rac1, a small GTP-binding protein widely implicated in actin cytoskeleton reorganization. This Guanine nucleotide Exchange Factor (GEF) is overexpressed in human luminal breast cancer, and its expression associates with disease progression, metastatic dissemination and poor outcome. Despite the established contribution of P-Rex1 to Rac activation and cell locomotion, whether this Rac-GEF has any relevant role in mitogenesis has been a subject of controversy. To tackle the discrepancies among various reports, we carried out an exhaustive analysis of the potential involvement of P-Rex1 on the activation of the mitogenic Erk pathway. Using a range of luminal breast cancer cellular models, we unequivocally showed that silencing P-Rex1 (transiently, stably, using multiple siRNA sequences) had no effect on the phospho-Erk response upon stimulation with growth factors (EGF, heregulin, IGF-I) or a GPCR ligand (SDF-1). The lack of involvement of P-Rex1 in Erk activation was confirmed at the single cell level using a fluorescent biosensor of Erk kinase activity. Depletion of P-Re...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research