| Autor: |
Lopez-Guerrero AM; Department of Biochemistry and Molecular Biology, School of Life Sciences and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain., Espinosa-Bermejo N; Department of Biochemistry and Molecular Biology, School of Life Sciences and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain., Sanchez-Lopez I; Department of Biochemistry and Molecular Biology, School of Life Sciences and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain., Macartney T; MRC- Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, United Kingdom., Pascual-Caro C; Department of Biochemistry and Molecular Biology, School of Life Sciences and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain., Orantos-Aguilera Y; Department of Biochemistry and Molecular Biology, School of Life Sciences and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain., Rodriguez-Ruiz L; Department of Cell Biology and Histology, University of Murcia, IMIB-Arrixaca, Murcia, 30100, Spain., Perez-Oliva AB; Department of Cell Biology and Histology, University of Murcia, IMIB-Arrixaca, Murcia, 30100, Spain., Mulero V; Department of Cell Biology and Histology, University of Murcia, IMIB-Arrixaca, Murcia, 30100, Spain., Pozo-Guisado E; Department of Cell Biology, School of Medicine and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain. epozo@unex.es., Martin-Romero FJ; Department of Biochemistry and Molecular Biology, School of Life Sciences and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, 06006, Spain. fjmartin@unex.es. |
| Abstrakt: |
Tumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca 2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca 2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo. |
