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Transforming growth factor-β-induced cell plasticity in liver fibrosis and hepatocarcinogenesis
Fabregat Romero, Isabel; Caballero-Diaz, Daniel
Universitat de Barcelona
The Transforming Growth Factor-beta (TGF-β) family plays relevant roles in the regulation of different cellular processes that are essential for tissue and organ homeostasis. In the case of the liver, TGF-β signaling participates in different stages of disease progression, from initial liver injury toward fibrosis, cirrhosis and cancer. When a chronic injury takes place, mobilization of lymphocytes and other inflammatory cells occur, thus setting the stage for persistence of an inflammatory response. Macrophages produce profibrotic mediators, among them, TGF-β, which is responsible for activation -transdifferentiation- of quiescent hepatic stellate cells (HSC) to a myofibroblast (MFB) phenotype. MFBs are the principal source of extracellular matrix protein (ECM) accumulation and prominent mediators of fibrogenesis. TGF-β also mediates an epithelial-mesenchymal transition (EMT) process in hepatocytes that may contribute, directly or indirectly, to increase the MFB population. In hepatocarcinogenesis, TGF-β plays a dual role, behaving as a suppressor factor at early stages, but contributing to later tumor progression, once cells escape from its cytostatic effects. As part of its potential pro-tumorigenic actions, TGF-β induces EMT in liver tumor cells, which increases its pro-migratory and invasive potential. In parallel, TGF-β also induces changes in tumor cell plasticity, conferring properties of a migratory tumor initiating cell (TIC). The main aim of this review is to shed light about the pleiotropic actions of TGF-β that explain its effects on the different liver cell populations. The cross-talk with other signaling pathways that contribute to TGF-β effects, in particular the Epidermal Growth Factor Receptor (EGFR), will be presented. Finally, we will discuss the rationale for targeting the TGF-β pathway in liver pathologies.
-Càncer
-Cèl·lules hepàtiques
-Fetge
-Plasticitat
-Cancer
-Liver cells
-Liver
-Plasticity
cc-by (c) Fabregat Romero, Isabel et al., 2018
http://creativecommons.org/licenses/by/3.0/es
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Frontiers Media
         

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Moreno Càceres, Joaquim; Caballero-Diaz, Daniel; Chike Nwosu, Zeribe; Meyer, Christoph; López Luque, Judit; Malfettone, Andrea; Lastra, Raquel; Serrano Piñol, M. Teresa; Ramos Rubio, Emilio; Dooley, Steven; Fabregat Romero, Isabel
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Moreno Càceres, Joaquim; Caballero-Diaz, Daniel; Chike Nwosu, Zeribe; Meyer, Christoph; López Luque, Judit; Malfettone, Andrea; Lastra, Raquel; Serrano Piñol, M. Teresa; Ramos Rubio, Emilio; Dooley, Steven; Fabregat Romero, Isabel
Moreno Càceres, Joaquim; Caballero-Diaz, Daniel; Chike Nwosu, Zeribe; Meyer, Christoph; López Luque, Judit; Malfettone, Andrea; Lastra, Raquel; Serrano Piñol, M. Teresa; Ramos Rubio, Emilio; Dooley, Steven; Fabregat Romero, Isabel