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C3G: A new player in the regulation of glioblastoma initiation and progression

AutorManzano Figueroa, Sara; Sequera, Celia; Baquero, Cristina; Palao, Nerea; Arechederra, María; Guerrero Arroyo, María del Carmen ; Porras, Almudena
Fecha de publicación2017
CitaciónFEBS3+ (2017)
XL SEBBM Congress (2017)
ResumenC3G is a guanine-nucleotide exchange factor (GEF) for Rap-1, although it can act through GEF independent mechanisms. The role of C3G in human cancer is controversial, acting as either a tumour suppressor or mediator depending on the cell context. Similarly, C3G can also play a dual role in migration. In colon carcinoma cells, we found that C3G represses migration and invasion through downregulation of p38α MAPK activity and promotes tumor growth. In this study, we have analyzed the function of C3G in human glioblastoma (GBM) through permanent gene silencing, using the U87 cell line as an in vitro model. Previous data from our group indicate that C3G knock-down enhances migration and invasion and induces actin cytoskeleton reorganization. These changes are accompanied by an increase in the expression of transcription factors and proteins involved in the epithelial-mesenchymal transition. Moreover, C3G knock-down induces anchorage-dependent and –independent growth, modifying cell organization within the foci. C3G silencing also modifi es the activity of different signaling pathways, such as p38MAPK or ERKs cascades, which play a role mediating C3G eff ects on cell adhesion, invasion and tumorigenesis. Interestingly, C3G depletion prevents c-Met activation and reduces that of EGFR, two essential tyrosine Kinase receptors (RTKs) in the onset and development of glioblastoma. The negative regulation of these RTKs in the absence of C3G impairs the activation of their downstream pathways in response to HGF or EGF, blocking HGF-induced invasion. C3G appears also to regulate stemness in GBM. C3G levels change during the acquisition of a glioblastoma initiating cell-like phenotype. Moreover, low C3G levels may favor the expression of stem markers and the intrinsic capacity of GICs to generate spheres in Extreme Limiting Dilution Assays. All these data indicate that C3G is an important regulator of glioblastoma initiation, progression and generation of metastasis. However, more studies are required to fully characterize C3G function in glioblastoma and its relevance in clinic.
DescripciónResumen del póster presentado al 1st Joint Meeting of the French-Portuguese-Spanish Biochemical and Molecular Biology Societies y al XL Spanish Society of Biochemistry and Molecular Biology (SEBBM) Congress, celebrado en Barcelona (España) del 23 al 26 de octubre de 2017.
Aparece en las colecciones: (IBMCC) Comunicaciones congresos
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