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Title

Mechanisms involved in the regulation of the tumorigenic and invasive properties of colon carcinoma cells by C3G

AuthorsPriego, Neibla; Sequera, Celia; Arechederra, María; Peña, Isabel; Manzano Figueroa, Sara; Martín-Granado, Víctor; Guerrero Arroyo, María del Carmen ; Porras, Almudena
Issue Date2015
CitationXXXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular (2015)
AbstractC3G is a guanine nucleotide exchange factor (GEF) for some Ras and Rho GTPases, mainly Rap-1. Nevertheless, it also acts through mechanisms independent of its GEF activity. It is essential for embryonic development due to its role on adhesion. C3G regulates several cellular functions such as proliferation, survival and migration. Its function in human cancer is controversial, acting as either a tumour suppressor or promoter depending on the context. p38 MAPKs are activated by several stimuli. They regulate different cellular functions, including migration and invasion. p38(alfa) MAPK is the most abundant isoform, which is essential for embryonic development. It plays a dual role in cancer, acting as a tumour suppressor in initial stages, but promoting migration, invasion and survival at later stages. We have previously identifi ed a functional interaction between C3G and p38a that controls cell death in mouse embryonic fibroblasts and also in chronic myeloid leukemia cells, where C3G-p38a pathway additionally regulates cell adhesion. We have now found that this C3G/p38a cascade also regulates migration and invasion of HCT116 colon carcinoma cells. Thus, C3G knock-down promotes migration/invasion through the enhancement of p38a activation by a Rap-1 independent pathway. We are analyzing if this pro-migratory effect is a consequence of an epithelial to mesenchymal transition (EMT) by measuring different EMT markers. Additionally, our in vitro and in vivo studies have revealed that both C3G and p38a promote tumour growth. Cytokines generated by colon carcinoma cells might indirectly lead to the regulation of tumour growth through its impact on the stroma.
DescriptionResumen del trabajo presentado al XXXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Valencia del 7 al 10 de septiembre de 2015.
URIhttp://hdl.handle.net/10261/180893
Appears in Collections:(IBMCC) Comunicaciones congresos
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