scholarly journals The Role of Bmp- and Fgf Signaling Modulating Mouse Proepicardium Cell Fate

2022 ◽  
Vol 9 ◽  
Author(s):  
Carlos Garcia-Padilla ◽  
Francisco Hernandez-Torres ◽  
Estefania Lozano-Velasco ◽  
Angel Dueñas ◽  
Maria del Mar Muñoz-Gallardo ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Family Members ◽  
Fgf Signaling ◽  
Differentiation Markers ◽  
Mesenchymal Transition ◽  
Endocardial Cell ◽  
Species Specific

Bmp and Fgf signaling are widely involved in multiple aspects of embryonic development. More recently non coding RNAs, such as microRNAs have also been reported to play essential roles during embryonic development. We have previously demonstrated that microRNAs, i.e., miR-130, play an essential role modulating Bmp and Fgf signaling during early stages of cardiomyogenesis. More recently, we have also demonstrated that microRNAs are capable of modulating cell fate decision during proepicardial/septum transversum (PE/ST) development, since over-expression of miR-23 blocked while miR-125, miR-146, miR-223 and miR-195 enhanced PE/ST-derived cardiomyogenesis, respectively. Importantly, regulation of these microRNAs is distinct modulated by Bmp2 and Fgf2 administration in chicken. In this study, we aim to dissect the functional role of Bmp and Fgf signaling during mouse PE/ST development, their implication regulating post-transcriptional modulators such as microRNAs and their impact on lineage determination. Mouse PE/ST explants and epicardial/endocardial cell cultures were distinctly administrated Bmp and Fgf family members. qPCR analyses of distinct microRNAs, cardiomyogenic, fibrogenic differentiation markers as well as key elements directly epithelial to mesenchymal transition were evaluated. Our data demonstrate that neither Bmp2/Bmp4 nor Fgf2/Fgf8 signaling is capable of inducing cardiomyogenesis, fibrogenesis or inducing EMT in mouse PE/ST explants, yet deregulation of several microRNAs is observed, in contrast to previous findings in chicken PE/ST. RNAseq analyses in mouse PE/ST and embryonic epicardium identified novel Bmp and Fgf family members that might be involved in such cell fate differences, however, their implication on EMT induction and cardiomyogenic and/or fibrogenic differentiation is limited. Thus our data support the notion of species-specific differences regulating PE/ST cardiomyogenic lineage commitment.

scholarly journals Prognostic Role of the MicroRNA-200 Family in Various Carcinomas: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jung Soo Lee ◽  
Young-Ho Ahn ◽  
Hye Sung Won ◽  
Der Sheng Sun ◽  
Yeo Hyung Kim ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Meta Analysis ◽  
Family Members ◽  
Progression Free Survival ◽  
Tissue Expression ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
Hazard Ratios ◽  
Cancer Types

Background/Aims.The miRNA-200 (miR-200) family may act as key inhibitors of epithelial-to-mesenchymal transition. However, the potential prognostic value of miR-200s in various human malignancies remains controversial. This meta-analysis analyzed the associations between miR-200 levels and survival outcomes in a variety of tumors.Methods.Eligible published studies were identified by searching the Embase, PubMed, CINAHL, and Google scholar databases. Patient clinical data were pooled, and pooled hazard ratios (HRs) with 95% confidence intervals (95% CI) were used to calculate the strength of this association.Results.The pooled HRs suggested that high tissue expression of miR-200 family members was associated with better survival (overall survival [OS]: HR = 0.70, 95% CI 0.54–0.91; progression-free survival [PFS]: HR = 0.63, 95% CI 0.52–0.76) in thirty-four eligible articles. In contrast, higher expression of circulating miR-200 members was significantly associated with poor clinical outcome (OS, HR = 1.68, 95% CI 1.15–2.46; PFS, HR = 2.62, 95% CI 1.68–4.07).Conclusion.The results from this meta-analysis suggest that miR-200 family members are potential prognostic biomarkers in patients with various carcinomas. To apply these findings in the clinic, large prospective studies are needed to validate the prognostic values of miR-200s in individual cancer types.

scholarly journals Craniofacial transitions: the role of EMT and MET during head development

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev196030
Author(s):  
Natalie J. Milmoe ◽  
Abigail S. Tucker
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cells ◽  
Molecular Changes ◽  
Mesenchymal Transition ◽  
Head Development ◽  
Mesenchymal To Epithelial Transition

ABSTRACTWithin the developing head, tissues undergo cell-fate transitions to shape the forming structures. This starts with the neural crest, which undergoes epithelial-to-mesenchymal transition (EMT) to form, amongst other tissues, many of the skeletal tissues of the head. In the eye and ear, these neural crest cells then transform back into an epithelium, via mesenchymal-to-epithelial transition (MET), highlighting the flexibility of this population. Elsewhere in the head, the epithelium loses its integrity and transforms into mesenchyme. Here, we review these craniofacial transitions, looking at why they happen, the factors that trigger them, and the cell and molecular changes they involve. We also discuss the consequences of aberrant EMT and MET in the head.

scholarly journals lncRNA HOTAIR Overexpression Induced Downregulation of c-Met Signaling Promotes Hybrid Epithelial/Mesenchymal Phenotype in Hepatocellular Carcinoma Cells

2020 ◽  
Author(s):  
Hande Topel ◽  
Ezgi Bagirsakci ◽  
Dehan Comez ◽  
Gulsun Bagci ◽  
Gulcin Cakan-Akdogan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Biological Significance ◽  
Metastatic Potential ◽  
Mesenchymal Transition ◽  
Lncrna Hotair

Abstract Background: Epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) are both reversible processes, and regulation of phenotypical transition is very important for progression of several cancers including hepatocellular carcinoma (HCC). Recently, it is defined that cancer cells can attain a hybrid epithelial/mesenchymal (hybrid E/M) phenotype. Cells with hybrid E/M phenotype comprise mixed epithelial and mesenchymal properties, they can be more resistant to therapeutics and also more capable of initiating metastatic lesions. However, the mechanisms regulating hybrid E/M in HCC are not well described yet. In this study, we investigated the role of the potential crosstalk between lncRNA HOTAIR and c-Met receptor tyrosine kinase, which are two essential regulators of EMT and MET, in acquiring of hybrid E/M phenotype in HCC. Methods: Expression of c-Met and HOTAIR were defined in HCC cell lines and patient tissues through HCC progression. lncRNA HOTAIR was overexpressed in SNU-449 cells and its effects on c-Met signaling were analyzed. c-Met was overexpressed in SNU-398 cells and its effect on HOTAIR expression was analyzed. Biological significance of HOTAIR/c-Met interplay was defined in means of adhesion, proliferation, motility behavior, invasion, spheroid formation and metastatic ability. Effect of ectopic HOTAIR expression on phenotype was defined with investigation of molecular epithelial and mesenchymal traits. Results: In vitro and in vivo experiments verified the pivotal role of lncRNA HOTAIR in acquisition of hybrid E/M phenotype through modulating expression and activation of c-Met and its membrane co-localizing partner Caveolin-1, and membrane organization to cope with the rate limiting steps of metastasis such as survival in adhesion independent microenvironment, escaping from anoikis and resisting to fluidic shear stress (FSS) in HCC. Conclusions: Our work provides the first evidence suggesting a role for lncRNA HOTAIR in the modulation of c-Met to promote hybrid E/M phenotype. The balance between lncRNA HOTAIR and c-Met might be critical for cell fate decision and metastatic potential of HCC cells.

Recent insights into the role of Notch signaling in tumorigenesis

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2223-2233 ◽  
Author(s):  
Kevin G. Leong ◽  
Aly Karsan
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Cellular Functions ◽  
Cellular Mechanisms ◽  
Transmembrane Receptors ◽  
Mesenchymal Transition ◽  
Functional Aspects ◽  
Solid Malignancies

AbstractMembers of the Notch family of transmembrane receptors play an important role in cell fate determination. Over the past decade, a role for Notch in the pathogenesis of hematologic and solid malignancies has become apparent. Numerous cellular functions and microenvironmental cues associated with tumorigenesis are modulated by Notch signaling, including proliferation, apoptosis, adhesion, epithelial-to-mesenchymal transition, and angiogenesis. It is becoming increasingly evident that Notch signaling can be both oncogenic and tumor suppressive. This review highlights recent findings regarding the molecular and functional aspects of Notch-mediated neoplastic transformation. In addition, cellular mechanisms that potentially explain the complex role of Notch in tumorigenesis are discussed.

scholarly journals The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5874
Author(s):  
Ilaria Cavallari ◽  
Francesco Ciccarese ◽  
Evgeniya Sharova ◽  
Loredana Urso ◽  
Vittoria Raimondi ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Family Members ◽  
Chromosome 1 ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Evolutionarily Conserved ◽  
Epithelial Phenotype ◽  
Human Chromosome 1

The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.

scholarly journals HOTAIR promotes an epithelial-to-mesenchymal transition through relocation of the histone demethylase Lsd1

2019 ◽  
Author(s):  
Julien Jarroux ◽  
Claire Bertrand ◽  
Marc Gabriel ◽  
Dominika Foretek ◽  
Zohra Saci ◽  
...  
Keyword(s):  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Histone Demethylase ◽  
Gene Promoters ◽  
Mesenchymal Transition ◽  
Epigenetic Regulator ◽  
Development And Differentiation ◽  
Lysine Demethylase ◽  
Truncated Variants

SummaryEpithelial-to-mesenchymal transition (EMT) drives a loss of epithelial traits by neoplastic cells enabling metastasis and recurrence in cancer. HOTAIR emerged as one of the most renowned long noncoding RNAs promoting EMT mostly as a scaffold for PRC2 and repressive histone H3 Lys27 methylation at gene promoters. In addition to PRC2, HOTAIR interacts with the Lsd1 lysine demethylase, a known epigenetic regulator of cell fate during development and differentiation. However, Lsd1 role in HOTAIR function is still poorly understood. Here, through expression of truncated variants of HOTAIR, we revealed that, in contrast to PRC2, its Lsd1-interacting domain is essential for acquisition of migratory properties by epithelial cells. HOTAIR induces Lsd1 relocation from its inherent genomic loci hence reprogramming the epithelial transcriptome. Our results uncovered an unexpected role of HOTAIR in EMT as an Lsd1 effector and pointed to the importance of Lsd1 as a guardian of the epithelial identity.

What we can learn from embryos to understand the mesenchymal-to-epithelial transition in tumor progression

2021 ◽  
Vol 478 (9) ◽  
pp. 1809-1825
Author(s):  
Yanel Bernardi ◽  
Pablo Hernán Strobl-Mazzulla
Keyword(s):  
Embryonic Development ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Early Embryonic Development ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Epithelial Plasticity ◽  
Major Attention ◽  
Post Transcriptional Regulation

Epithelial plasticity involved the terminal and transitional stages that occur during epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET), both are essential at different stages of early embryonic development that have been co-opted by cancer cells to undergo tumor metastasis. These processes are regulated at multiple instances, whereas the post-transcriptional regulation of key genes mediated by microRNAs is gaining major attention as a common and conserved pathway. In this review, we focus on discussing the latest findings of the cellular and molecular basis of the less characterized process of MET during embryonic development, with special attention to the role of microRNAs. Although we take in consideration the necessity of being cautious when extrapolating the obtained evidence, we propose some commonalities between early embryonic development and cancer progression that can shed light into our current understanding of this complex event and might aid in the design of specific therapeutic approaches.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

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