RT Journal Article
T1 HGF/c-Met signaling promotes liver progenitor cell migration and invasion by an epithelial-mesenchymal transition-independent, phosphatidyl inositol-3 kinase-dependent pathway in an in vitro model
A1 Suárez Causado, Amileth
A1 Caballero Díaz, D.
A1 Bertrán, E.
A1 Roncero Romero, César
A1 Addante, Annalisa
A1 García Álvaro, M.
A1 Fernández García de Castro, M.
A1 Herrera González, Blanca
A1 Porras Gallo, Almudena
A1 Fabregat, I.
A1 Sánchez Muñoz, Aránzazu
AB Oval cells constitute an interesting hepatic cell population. They contribute to sustain liver regeneration during chronic liver damage, but in doing this they can be target of malignant conversion and become tumor-initiating cells and drive hepatocarcinogenesis. The molecular mechanisms beneath either their pro-regenerative or pro-tumorigenic potential are still poorly understood. In this study, we have investigated the role of the HGF/c-Met pathway in regulation of oval cell migratory and invasive properties. Our results show that HGF induces c-Met-dependent oval cell migration both in normal culture conditions and after in vitro wounding. HGF-triggered migration involves Factin cytoskeleton reorganization, which is also evidenced by activation of Rac1. Furthermore, HGF causes ZO-1 translocation from cell-cell contact sites to cytoplasm and its concomitant activation by phosphorylation. However, no loss of expression of cell-cell adhesion proteins, including E-cadherin, ZO-1 and Occludin-1, is observed. Additionally, migration does not lead to cell dispersal but to a characteristic organized pattern in rows, in turn associated with Golgi compaction, providing strong evidence of a morphogenic collective migration. Besides migration, HGF increases oval cell invasion through extracellular matrix, process that requires PI3K activation and is at least partly mediated by expression and activation of metalloproteases. Altogether, our findings provide novel insights into the cellular and molecular mechanisms mediating the essential role of HGF/c-Met signaling during oval cell-mediated mouse liver regeneration.
PB Elsevier
SN 0167-4889
YR 2015
FD 2015-07-21
LK https://hdl.handle.net/20.500.14352/24093
UL https://hdl.handle.net/20.500.14352/24093
LA eng
NO Unión Europea. FP7
NO Ministerio de Economía y Competitividad (MINECO)
NO UCM Research Funding
NO People Programme (Marie Curie Actions)
DS Docta Complutense
RD 29 abr 2024