RESUMO
Epithelial Mesenchymal Transition (EMT) is a dedifferentiation process implicated in many physio-pathological conditions including tumor transformation. EMT is regulated by several extracellular mediators and under certain conditions it can be reversible. Autophagy is a conserved catabolic process in which intracellular components such as protein/DNA aggregates and abnormal organelles are degraded in specific lysosomes. In cancer, autophagy plays a controversial role, acting in different conditions as both a tumor suppressor and a tumor-promoting mechanism. Experimental evidence shows that deep interrelations exist between EMT and autophagy-related pathways. Although this interplay has already been analyzed in previous studies, understanding mechanisms and the translational implications of autophagy/EMT need further study. The role of autophagy in EMT is not limited to morphological changes, but activation of autophagy could be important to DNA repair/damage system, cell adhesion molecules, and cell proliferation and differentiation processes. Based on this, both autophagy and EMT and related pathways are now considered as targets for cancer therapy. In this review article, the contribution of autophagy to EMT and progression of cancer is discussed. This article also describes the multiple connections between EMT and autophagy and their implication in cancer treatment.
RESUMO
The liver is an organ that is particularly exposed to reactive oxygen species (ROS), which not only arise during metabolic functions but also during the biotransformation of xenobiotics. The disruption of redox balance causes oxidative stress, which affects liver function, modulates inflammatory pathways and contributes to disease. Thus, oxidative stress is implicated in acute liver injury and in the pathogenesis of prevalent infectious or metabolic chronic liver diseases such as viral hepatitis B or C, alcoholic fatty liver disease, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Moreover, oxidative stress plays a crucial role in liver disease progression to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Herein, we provide an overview on the effects of oxidative stress on liver pathophysiology and the mechanisms by which oxidative stress promotes liver disease.
RESUMO
OBJECTIVES: TGF-ß through hyperelongation of glycosaminoglycan (GAG) chains leads to binding of low-density lipoproteins to the proteoglycans. The vasoactive peptide, endothelin-1 (ET-1), plays a key role in the development of atherosclerosis. This study addressed the question whether ET-1 by activating the Rho kinase and cytoskeletal rearrangement can transactivate the TGF-ß receptor leading to phosphorylation of the transcription factor Smad2 and increased expression of the GAG chain synthesizing enzyme such as chondroitin synthase-1 (CHSY-1) in bovine aortic endothelial cells (BAECs). METHODS: In this study, intermediates in ET-1-induced Smad2C phosphorylation and the protein level of CHSY-1 were identified and quantified by Western blotting. KEY FINDINGS: Endothelin-1 caused time-dependent phosphorylation of Smad2C which was inhibited in the presence of the endothelin B receptor antagonist, BQ788. The response to ET-1 was inhibited by the Rho/ROCK kinase antagonist, Y27632 and by cytochalasin D, an inhibitor of actin polymerization but the ET-1-mediated pSmad2C was not inhibited by the matrix metalloproteinase (MMP) inhibitor, GM6001. ET-1 increased CHSY-1 protein level, which was inhibited in the presence of BQ788, cytochalasin D and Y27632. CONCLUSIONS: Endothelin-1 signalling via the ETB receptor utilizes cytoskeletal rearrangement and Rho kinase but not MMPs leading to TßRI transactivation signalling and phosphorylation of Smad2C and through this pathway increased the level of CHSY-1.
