1,721,026 research outputs found
Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression
Full text linkGrowing evidence points to exosomes as key mediators of cell−cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated intercellular communication in tumor-niche establishment, migration, invasion, and metastasis processes. This body of evidence suggests the relevance of taking into account exosome-mediated signaling and its multifaceted aspects to develop innovative anti-tumoral therapeutic approaches
"Epigenetic Regulation in Hepatocellular Carcinoma Requires Long Noncoding RNAs"
Full text linkRecent evidence has proven the relevance of epigenetic changes in the development of hepatocellular carcinoma (HCC), the major adult liver malignancy. Moreover, HCC onset and progression correlates with the deregulation of several long non-coding RNAs (lncRNAs), exhibiting great biological significance. As discussed in this review, many of these transcripts are able to specifically act as tumor suppressors or oncogenes by means of their role as molecular platforms. Indeed, these lncRNAs are able to bind and recruit epigenetic modifiers on specific genomic loci, ultimately resulting in regulation of the gene expression relevant in cancer development.
The evidence presented in this review highlights that lncRNAs-mediated epigenetic regulation should be taken into account for potential targeted therapeutic approaches
“Molecular Mechanisms Controlling EMT/MET Oscillation during Hepatic Stem Renewal and Differentiation”
No full text"MOLECULAR MECHANISM CONTROLLING EMT/MET OSCILLATIONS AND HEPATOCYTE DIFFERENTIATION OF RESIDENT LIVER STEM CELLS (RLSCS)".
No full textSelected presentation from submitted (poster) abstracts
The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil
No full textInhibition of MMH (Met Murine Hepatocyte) cell differentiation by TGFbeta is abrogated by pre-treatment with the heritable differentiation effector FGF1
No full textMMH (Met murine hepatocyte) liver cells derived from transgenic mice expressing a truncated constitutively active form of human c-Met are non-transformed immortalized cell lines. We have previously shown that they harbor: (1) epithelial cells that express the liver-enriched transcription factors HNF4 and HNF1 alpha, and that can be stably induced by FGF1 to express liver functions, and (2) fibroblast-like bi-potential palmate cells that can differentiate into bile duct-like structures in Matrigel cultures, or into epithelial cells competent to express hepatic functions. Low concentrations of TGF beta have been found to inhibit growth and differentiation of MMH cells. The factor stabilized the palmate cell phenotype, and it provoked epithelial cells to acquire palmate-like morphological characteristics, in parallel with down-regulation of expression of HNF4 and HNF1 alpha and activation of Snail transcripts. The effects of TGF beta were dominant if it was added with FGF1, but the effects on differentiation were abrogated if cells had been pre-treated with FGF1, This work identifies TGF beta as a factor that could be implicated in maintaining bi-potential precursor cells in the liver, FGF1 as one that could override the TGF beta effects and Snail as a candidate for mediation of the signal
The lncRNA HOTAIR links the repressor Snail to epigenetic modifications of specific genomic sites in Epithelial-to-Mesenchymal Transition
No full textThe lncRNA HOTAIR links the repressor Snail to epigenetic modifications of specific genomic sites in Epithelial-to-Mesenchymal Transition
Cecilia Battistelli 1,§, Carla Cicchini 1,§,, Laura Santangelo 1, Anna Tramontano 2, Marco Tripodi 1,3
1Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy
2Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Physics, Sapienza University of Rome, Rome, Italy
3National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
§Co-first authors.
Co-corresponding authors
The transcription factor Snail is a master regulator of cellular identity and Epithelial-to-Mesenchymal Transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail specific binding sites is unclear. Here we report that the long non-coding (lnc)RNA HOTAIR mediates a physical interaction between Snail and EZH2, enzymatic subunit of the Polycomb Repressive Complex 2 (PRC2) and main writer of chromatin repressive marks. The Snail repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate a lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT
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