RT Journal Article
T1 C3G down-regulation enhances pro-migratory and stemness properties of oval cells by promoting an epithelial-mesenchymal-like process
A1 Palao, Nerea
A1 Sequera, Celia
A1 Cuesta Martínez, Ángel
A1 Baquero, Cristina
A1 Bragado Domingo, Paloma
A1 Gutiérrez Uzquiza, Álvaro
A1 Sánchez Muñoz, Aranzazu
A1 Guerrero, Carmen
A1 Porras Gallo, María Almudena
AB Previous data indicate that C3G (RapGEF1) main isoform is highly expressed in liver progenitor cells (or oval cells) compared to adult mature hepatocytes, suggesting it may play an important role in oval cell biology. Hence, we have explored C3G function in the regulation of oval cell properties by permanent gene silencing using shRNAs. We found that C3G knock-down enhanced migratory and invasive ability of oval cells by promoting a partial epithelial to mesenchymal transition (EMT). This is likely mediated by upregulation of mRNA expression of the EMT-inducing transcription factors, Snail1, Zeb1 and Zeb2, induced in C3G-silenced oval cells. This EMT is associated to a higher expression of the stemness markers, CD133 and CD44. Moreover, C3G down-regulation increased oval cells clonogenic capacity by enhancing cell scattering. However, C3G knock-down did not impair oval cell differentiation into hepatocyte lineage. Mechanistic studies revealed that HGF/MET signaling and its pro-invasive activity was impaired in oval cells with low levels of C3G, while TGF-β signaling was increased. Altogether, these data suggest that C3G might be tightly regulated to ensure liver repair in chronic liver diseases such as non-alcoholic steatohepatitis. Hence, reduced C3G levels could facilitate oval cell expansion, after the proliferation peak, by enhancing migration.
PB IVYSPRING INTERNATIONAL PUBLISHER
SN 1449-2288
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/115498
UL https://hdl.handle.net/20.500.14352/115498
LA eng
NO Palao N, Sequera C, Cuesta AM, Baquero C, Bragado P, Gutierrez-Uzquiza A, Sánchez A, Guerrero C, Porras A. C3G down-regulation enhances pro-migratory and stemness properties of oval cells by promoting an epithelial-mesenchymal-like process. Int J Biol Sci 2022 June; 18(15): 5873-5884.
NO Ministerio de Economía y Competitividad (España)
NO Junta de Castilla y León
NO European Commission
NO Ministerio de Educación y Cultura (España)
NO Universidad Complutense de Madrid
NO Comunidad de Madrid
DS Docta Complutense
RD 18 jul 2025