RT Journal Article
T1 C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms
A1 Priego, Neibla
A1 Arechederra, María
A1 Sequera Hurtado, Celia
A1 Bragado Domingo, Paloma
A1 Vázquez-Carballo, Ana
A1 Gutiérrez Uzquiza, Álvaro
A1 Martín-Granado, Víctor
A1 Ventura, Juan José
A1 Kazanietz, Marcelo G.
A1 Carmen Guerrero, Marcelo G.
A1 Porras Gallo, María Almudena
AB C3G, a Guanine nucleotide Exchange Factor (GEF) for Rap1 and R-Ras, has been shown to play important roles in development and cancer. Previous studies determined that C3G regulates cell death through down-regulation of p38α MAPK activity. Here, we found that C3G knock-down in MEFs and HCT116 cells promotes migration and invasion through Rap1-mediated p38α hyper-activation. These effects of C3G were inhibited by Rap1 knock-down or inactivation. The enhanced migration observed in C3G depleted HCT116 cells was associated with reduction in E-cadherinexpression, internalization of ZO-1, actin cytoskeleton reor ganization and decreased adhesion. We also found that matrix metalloproteases MMP2 and MMP9 are involved in the pro-invasive effect of C3G down-regulation. Additionally, our studies revealed that both C3G and p38α collaborate to promote growth of HCT116 cells in vitro and in vivo, possibly by enhancing cell survival. In fact, knocking-down C3G or p38α individually or together promoted cell death in vitro, although only the double C3Gp38α silencing was able to increase cell death within tum ors. Notably, we found that the pro-tumorigenic function of C3G does not depend on p38α or Rap1 activation. Altogether, our studies uncover novel mechanisms by which C3G controls key aspects of tumorigenesis.
SN 1949-2553
YR 2016
FD 2016-06-07
LK https://hdl.handle.net/20.500.14352/115809
UL https://hdl.handle.net/20.500.14352/115809
LA eng
NO Priego N, Arechederra M, Sequera C, Bragado P, Vázquez-Carballo A, Gutiérrez-Uzquiza Á, et al. C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms. Oncotarget [Internet]. 19 de julio de 2016 [citado 23 de enero de 2025];7(29):45060-78. Disponible en: https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.9911
NO Cellex Foundation
NO Ministerio de Economía y Competitividad (España)
NO Universidad Complutense de Madrid
NO Consejería de Educación (Castilla y León)
NO FEDER
NO Ministerio de Educación y Cultura (España)
DS Docta Complutense
RD 9 abr 2025