Influenza A Potentiates The Pulmonary Fibrotic Response Through Epigenetic Regulation Of Epithelial To Mesenchymal Transition

Metastasis is the end stage of cancer progression and the direct cause of most cancer-related deaths. The spreading of cancer cells from the primary site to distant organs is a multistep process known as the metastatic cascade, including local invasion, intravasation, survival in the circulation, extravasation, and colonization. Each of these steps is driven by the acquisition of genetic and/or epigenetic alterations within cancer cells, leading to subsequent transformation of metastatic cells. Epithelial–mesenchymal transition (EMT), a cellular process mediating the conversion of cell from epithelial to mesenchymal phenotype, and its reverse transformation, termed mesenchymal–epithelial transition (MET), together endow metastatic cells with traits needed to generate overt metastases in different scenarios. The dynamic shift between these two phenotypes and their transitional state, termed partial EMT, emphasizes the plasticity of EMT. Recent advances attributed this plasticity to epigenetic regulation, which has implications for the therapeutic targeting of cancer metastasis. In this review, we will discuss the association between epigenetic events and the multifaceted nature of EMT, which may provide insights into the steps of the cancer metastatic cascade.

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Epigenetic regulation of TGF-β1 signalling in dilative aortopathy of the thoracic ascending aorta

Clinical Science ◽

10.1042/cs20160222 ◽

2016 ◽

Vol 130 (16) ◽

pp. 1389-1405 ◽

Cited By ~ 19

Author(s):

Amalia Forte ◽

Umberto Galderisi ◽

Marilena Cipollaro ◽

Marisa De Feo ◽

Alessandro Della Corte

Keyword(s):

Gene Expression ◽

Epigenetic Regulation ◽

Epithelial To Mesenchymal Transition ◽

Transforming Growth Factor ◽

Regulation Of Gene Expression ◽

Transforming Growth Factor Β1 ◽

Ascending Aorta ◽

Mesenchymal Transition ◽

Aorta Dilatation ◽

Tgf Β1

The term ‘epigenetics’ refers to heritable, reversible DNA or histone modifications that affect gene expression without modifying the DNA sequence. Epigenetic modulation of gene expression also includes the RNA interference mechanism. Epigenetic regulation of gene expression is fundamental during development and throughout life, also playing a central role in disease progression. The transforming growth factor β1 (TGF-β1) and its downstream effectors are key players in tissue repair and fibrosis, extracellular matrix remodelling, inflammation, cell proliferation and migration. TGF-β1 can also induce cell switch in epithelial-to-mesenchymal transition, leading to myofibroblast transdifferentiation. Cellular pathways triggered by TGF-β1 in thoracic ascending aorta dilatation have relevant roles to play in remodelling of the vascular wall by virtue of their association with monogenic syndromes that implicate an aortic aneurysm, including Loeys–Dietz and Marfan's syndromes. Several studies and reviews have focused on the progression of aneurysms in the abdominal aorta, but research efforts are now increasingly being focused on pathogenic mechanisms of thoracic ascending aorta dilatation. The present review summarizes the most recent findings concerning the epigenetic regulation of effectors of TGF-β1 pathways, triggered by sporadic dilative aortopathy of the thoracic ascending aorta in the presence of a tricuspid or bicuspid aortic valve, a congenital malformation occurring in 0.5–2% of the general population. A more in-depth comprehension of the epigenetic alterations associated with TGF-β1 canonical and non-canonical pathways in dilatation of the ascending aorta could be helpful to clarify its pathogenesis, identify early potential biomarkers of disease, and, possibly, develop preventive and therapeutic strategies.

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Epigenetic Regulation of EMT (Epithelial to Mesenchymal Transition) and Tumor Aggressiveness: A View on Paradoxical Roles of KDM6B and EZH2

Epigenomes ◽

10.3390/epigenomes3010001 ◽

2018 ◽

Vol 3 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Camille Lachat ◽

Michaël Boyer-Guittaut ◽

Paul Peixoto ◽

Eric Hervouet

Keyword(s):

Cell Lines ◽

Epigenetic Regulation ◽

Epithelial To Mesenchymal Transition ◽

Target Genes ◽

Great Part ◽

Mesenchymal Transition ◽

Specific Subset ◽

Cancer Aggressiveness ◽

Cancer Types

EMT (epithelial to mesenchymal transition) is a plastic phenomenon involved in metastasis formation. Its plasticity is conferred in a great part by its epigenetic regulation. It has been reported that the trimethylation of lysine 27 histone H3 (H3K27me3) was a master regulator of EMT through two antagonist enzymes that regulate this mark, the methyltransferase EZH2 (enhancer of zeste homolog 2) and the lysine demethylase KDM6B (lysine femethylase 6B). Here we report that EZH2 and KDM6B are overexpressed in numerous cancers and involved in the aggressive phenotype and EMT in various cell lines by regulating a specific subset of genes. The first paradoxical role of these enzymes is that they are antagonistic, but both involved in cancer aggressiveness and EMT. The second paradoxical role of EZH2 and KDM6B during EMT and cancer aggressiveness is that they are also inactivated or under-expressed in some cancer types and linked to epithelial phenotypes in other cancer cell lines. We also report that new cancer therapeutic strategies are targeting KDM6B and EZH2, but the specificity of these treatments may be increased by learning more about the mechanisms of action of these enzymes and their specific partners or target genes in different cancer types.

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Deregulation of Transcriptional Enhancers in Cancer

Cancers ◽

10.3390/cancers13143532 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3532

Author(s):

Fatemeh Mirzadeh Azad ◽

Yaser Atlasi

Keyword(s):

Epigenetic Regulation ◽

Adult Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Cell Plasticity ◽

Tumour Heterogeneity ◽

Mesenchymal Transition ◽

Transcriptional Enhancers ◽

Control Gene Expression ◽

Epigenetic Modifiers ◽

External Cues

Epigenetic regulations can shape a cell’s identity by reversible modifications of the chromatin that ultimately control gene expression in response to internal and external cues. In this review, we first discuss the concept of cell plasticity in cancer, a process that is directly controlled by epigenetic mechanisms, with a particular focus on transcriptional enhancers as the cornerstone of epigenetic regulation. In the second part, we discuss mechanisms of enhancer deregulation in adult stem cells and epithelial-to-mesenchymal transition (EMT), as two paradigms of cell plasticity that are dependent on epigenetic regulation and serve as major sources of tumour heterogeneity. Finally, we review how genetic variations at enhancers and their epigenetic modifiers contribute to tumourigenesis, and we highlight examples of cancer drugs that target epigenetic modifications at enhancers.

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