scholarly journals NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells

2019 ◽  
Author(s):  
P García-Gómez ◽  
M Dadras ◽  
C Bellomo ◽  
A Mezheyeuski ◽  
K Tzavlaki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Ros Production ◽  
Self Renewal ◽  
Glioblastoma Stem Cells ◽  
Nadph Oxidase 4

ABSTRACTGlioblastoma (GBM) is the most aggressive and common glioma subtype with a median survival of 15 months after diagnosis. Current treatments have limited therapeutic efficacy, thus more effective approaches are needed. The glioblastoma tumoral mass is characterized by a small cellular subpopulation, the Glioblastoma stem cells (GSCs), which has been held accountant for initiation, invasion, proliferation, relapse and resistance to chemo- and radiotherapy. Targeted therapies against GSCs are crucial, and so is the understanding of the molecular mechanisms that govern the GSCs. Transforming growth factor β (TGFβ), platelet growth factor (PDGF) signalling and Reactive Oxygen Species (ROS) production govern and regulate cancer-stem cell biology. In this work, we focus on the role of the NADPH oxidase 4 (NOX4) downstream of TGFβ signalling in the GSCs. NOX4 utilises NADPH to generate ROS; TGFβ induces NOX4 expression, thus increasing ROS production. Interestingly, NOX4 itself regulates GSC self-renewal and modulates Since TGFβ regulates PDGFB in GSC, we analysed how PDGFB modulates NOX4 expression and increases ROS production. Both TGFβ and PDGF signalling regulate GSC proliferation in a NOX4/ROS-dependent manner. The transcription factor NRF2, involved in the transcriptional regulation of antioxidant and metabolic responses, is regulated by both TGFβ and NOX4. This results in an antioxidant response, which positively contributes to GSC self-renewal and proliferation. In conclusion, this work functionally establishes NOX4 as a key mediator of GSC biology.

scholarly journals Stem cells for cardiac regeneration and possible roles of the transforming growth factor-β superfamily

2012 ◽  
Vol 3 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Nanako Kawaguchi
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Cell Biology ◽  
Transforming Growth Factor ◽  
Methyl Cellulose ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Cardiac Stem Cells ◽  
Dependent Manner ◽  
Tgf Β1

AbstractHeart failure is a leading cause of death worldwide. Studies of stem cell biology are essential for developing efficient treatments. Recently, we established and characterized c-kit-positive cardiac stem cells from the adult rat heart. Using a MethoCult culture system with a methyl-cellulose-based medium, stem-like left-atrium-derived pluripotent cells could be regulated to differentiate into skeletal/cardiac myocytes or adipocytes with almost 100% purity. Microarray and pathway analyses of these cells showed that transforming growth factor-β1 (TGF-β1) and noggin were significantly involved in the differentiation switch. Furthermore, TGF-β1 may act as a regulator for this switch because it simultaneously inhibits adipogenesis and activates myogenesis in a dose-dependent manner. However, the effect of TGF-β varies with developmental stage, dosage, and timing of treatment. In the present review, the findings of recent studies, in particular the use of c-kit-positive cardiac stem cells, are discussed. The effects of the TGF-β superfamily on differentiation, especially on adipogenesis and/or myogenesis, have important implications for future regenerative medicine.

scholarly journals Wnt5a Signaling in Normal and Cancer Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Zhou ◽  
Thomas J. Kipps ◽  
Suping Zhang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Target Cells ◽  
Dependent Manner ◽  
Self Renewal ◽  
Surface Receptors ◽  
Canonical Wnt

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

STEM-14. THE WRAD COMPLEX REPRESENTS A THERAPEUTIC TARGET FOR CANCER STEM CELLS IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi23-vi24
Author(s):  
Kelly Mitchell ◽  
Joseph Alvarado ◽  
Christopher Goins ◽  
Steven Martinez ◽  
Jonathan Macdonald ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Self Renewal ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

Abstract Glioblastoma (GBM) progression and resistance to conventional therapies is driven in part by cells within the tumor with stem cell properties including quiescence, self-renewal and drug efflux potential. It is thought that eliminating these cancer stem cells (CSCs) is a key component to successful clinical management of GBM. However, currently, few known molecular mechanisms driving CSCs can be exploited for therapeutic development. Core transcription factors such as SOX2, OLIG2, OCT4 and NANOG maintain the CSC state in GBM. Our laboratory recently uncovered a self-renewal signaling axis involving RBBP5 that is necessary and sufficient for CSC maintenance through driving expression of these core stem cell maintenance transcription factors. RBBP5 is a component of the WRAD complex, which promotes Lys4 methylation of histone H3 to positively regulate transcription. We hypothesized that targeting RBBP5 could be a means to disrupt epigenetic programs that maintain CSCs in stemness transcriptional states. We found that genetic and pharmacologic inhibition of the WRAD complex reduced CSC growth, self-renewal and tumor initiation potential. WRAD inhibitors partially dissembled the WRAD complex and reduced H3K4 trimethylation both globally and at the promoters of key stem cell maintenance transcription factors. Using a CSC reporter system, we demonstrated that WRAD complex inhibition decreased growth of SOX2/OCT4 expressing CSCs in a concentration-dependent manner as quantified by live imaging. Overall, our studies assess the function of the WRAD complex and the effect of WRAD complex inhibitors in preclinical models and specifically on the stem cell state for the first time in GBM. Studying the functions of the WRAD complex in CSCs may improve understanding of GBM pathogenesis and elucidate how CSCs survive despite aggressive chemotherapy and radiation. Our ongoing studies aim to develop brain penetrant inhibitors targeting the WRAD complex as an anti-CSC strategy that could potentially synergize with standard of care treatments.

scholarly journals Transforming Growth Factor-β1 Induces Transdifferentiation of Myoblasts into Myofibroblasts via Up-Regulation of Sphingosine Kinase-1/S1P3 Axis

2010 ◽  
Vol 21 (6) ◽  
pp. 1111-1124 ◽  
Author(s):  
Francesca Cencetti ◽  
Caterina Bernacchioni ◽  
Paola Nincheri ◽  
Chiara Donati ◽  
Paola Bruni
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Rho Kinase ◽  
Sphingosine Kinase ◽  
Transforming Growth Factor Β1 ◽  
Dependent Manner ◽  
Muscle Fibrosis ◽  
Sphingosine 1 Phosphate

The pleiotropic cytokine transforming growth factor (TGF)-β1 is a key player in the onset of skeletal muscle fibrosis, which hampers tissue repair. However, the molecular mechanisms implicated in TGFβ1-dependent transdifferentiation of myoblasts into myofibroblasts are presently unknown. Here, we show that TGFβ1 up-regulates sphingosine kinase (SK)-1 in C2C12 myoblasts in a Smad-dependent manner, and concomitantly modifies the expression of sphingosine 1-phosphate (S1P) receptors (S1PRs). Notably, pharmacological or short interfering RNA-mediated inhibition of SK1 prevented the induction of fibrotic markers by TGFβ1. Moreover, inhibition of S1P3, which became the highest expressed S1PR after TGFβ1 challenge, strongly attenuated the profibrotic response to TGFβ1. Furthermore, downstream of S1P3, Rho/Rho kinase signaling was found critically implicated in the profibrotic action of TGFβ1. Importantly, we demonstrate that SK/S1P axis, known to play a key role in myogenesis via S1P2, consequently to TGFβ1-dependent S1PR pattern remodeling, becomes responsible for transmitting a profibrotic, antidifferentiating action. This study provides new compelling information on the mechanism by which TGFβ1 gives rise to fibrosis in skeletal muscle, opening new perspectives for its pharmacological treatment. Moreover, it highlights the pleiotropic role of SK/S1P axis in skeletal myoblasts that, depending on the expressed S1PR pattern, seems capable of eliciting multiple, even contrasting biological responses.

scholarly journals Immune Cell Induced Migration of Osteoprogenitor Cells Is Mediated by TGF-β Dependent Upregulation of NOX4 and Activation of Focal Adhesion Kinase

2018 ◽  
Vol 19 (8) ◽  
pp. 2239 ◽  
Author(s):  
Sabrina Ehnert ◽  
Caren Linnemann ◽  
Romina Aspera-Werz ◽  
Daria Bykova ◽  
Sara Biermann ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Conditioned Media ◽  
Dependent Manner ◽  
Osteoprogenitor Cells ◽  
Nadph Oxidase 4

The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and focal adhesion kinase (FAK) as possible regulators. Monocyte- and macrophage (THP-1 cells ± phorbol 12-myristate 13-acetate (PMA) treatment)-conditioned media, other than the granulocyte-conditioned medium (HL-60 cells + dimethyl sulfoxide (DMSO) treatment), induce migration of phOBs. Monocyte- and macrophage (THP-1 cells)-conditioned media activate Smad3-dependent TGF-β signaling in the phOBs. Stimulation with TGF-β promotes migration of phOBs. Furthermore, TGF-β treatment strongly induces NOX4 expression on both mRNA and protein levels. The associated reactive oxygen species (ROS) accumulation results in phosphorylation (Y397) of FAK. Blocking TGF-β signaling, NOX4 activity and FAK signaling effectively inhibits the migration of phOBs towards TGF-β. In summary, our data suggest that monocytic- and macrophage-like cells induce migration of phOBs in a TGF-β-dependent manner, with TGF-β-dependent induction of NOX4, associated production of ROS and resulting activation of FAK as key mediators.

Hematopoietic Stem Cells Overexpressing Smad7 Exhibit Increased Self-Renewal and Regeneration Capacity in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 561-561 ◽  
Author(s):  
Ulrika Blank ◽  
Jonas Larsson ◽  
Taiju Utsugisawa ◽  
Mattias Magnusson ◽  
Jenny Klintman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Internal Ribosomal Entry Site ◽  
Entry Site ◽  
Related Factors ◽  
Self Renewal ◽  
Hematopoietic Stem

Abstract The hematopoietic stem cell (HSC) resides in the bone marrow (BM) and can self-renew to generate more stem cells as well as differentiate into all hematopoietic lineages. The precise molecular mechanisms, which govern HSC fate decisions are poorly understood. The Transforming Growth Factor-β (TGF-β) superfamily of ligands, including the TGF-βs, Activins and Bone Morphogenetic Proteins (BMPs), encompasses an important group of growth factors, many of which have been shown to modulate and regulate hematopoiesis. Smad7 is known to block the phosphorylation event of receptor-activated Smads, thus creating a block in the entire signaling cascade downstream of TGF-β and related factors. To assess the effect of blocking the entire Smad signaling pathway downstream of TGF-β/Activin and BMP in HSCs in vivo, we have overexpressed the inhibitory Smad7 by a retroviral gene transfer approach. Both control and Smad7 vectors were MSCV based and expression was driven by the LTR promoter. The Smad7 vector contained the cDNA sequence for murine Smad7 and an internal ribosomal entry site (IRES) followed by GFP, whereas the control vector contained IRES and GFP only. In these experiments BM from wild type C57/B6 mice could efficiently be transduced with Smad7 or control vectors respectively. Upon transduction, cells (Ly5.2) were transplanted in a competitive fashion into lethally irradiated recipients (Ly5.1) and transduced cells were monitored by GFP fluorescence. Smad7 overexpressing cells were able to long-term reconstitute as well as give rise to both lymphoid and myeloid compartments at normal distributions. When self-renewal was assessed by secondary transplantations, Smad7 overexpressing cells showed significantly increased reconstitution ability compared to control transduced cells (blood samples at 12 weeks post transplant: 37.3 ± 5,9 for Smad7 vs. 5.06 ± 1,7 for control. Data represent % GFP positive cells ± SEM). Furthermore, Western blot analysis showed efficient expression of Smad7 protein in BM cells originating from transduced cells of transplanted mice. In addition, Smad2 and Smad1 phosphorylation was blocked upon TGF-β, Activin or BMP stimulation in BM cells, suggesting that Smad7 was functionally active in BM cells in vivo. However, when cultured under serum-free conditions in vitro, Smad7 overexpressing cells exhibited reduced proliferative capacity as compared to control transduced cells (3.5 times fewer cells by day 12 post transduction), suggesting that the in vivo phenotype was dependent on the BM microenvironment. Taken together, our data indicate that blocking of several TGF-β pathways simultaneously increases the self-renewal ability of HSCs in vivo, but not in vitro.

Redox Signaling in Adult Stem Cell Biology: A New Target Controlling Pluripotency and Differentiation. What about Iron Chelators?.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2299-2299
Author(s):  
Tiziana Tataranni ◽  
Francesca Agriesti ◽  
Carmela Mazzoccoli ◽  
Vitalba Ruggieri ◽  
Fiorella D'Auria ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Biology ◽  
Redox Signaling ◽  
Iron Chelators ◽  
Ros Production ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Functional Features ◽  
Mitochondrial Respiratory

Abstract Abstract 2299 Introduction Hematopoietic stem cells (HSCs) constitute a reservoir of undifferentiated cells that can be committed, upon appropriate stimuli, in the haematic lineages. Although residing in a bone-marrow hypoxic microenvironment (niche) and mainly relying on anaerobic glycolysis, HSCs are endowed with mitochondria. Recently, specific interest has been focused on HSCs mitochondria and on their role as reactive oxygen species (ROS) generators during the early phases of commitment. Indeed, consolidated evidences highlight the importance of redox signalling in the homeostasis of fundamental processes in cell adaptive biology and particularly in controlling the balance between self-renewal and differentiation of stem cells. HSCs constitutively generate low levels of ROS produced by both mitochondrial respiratory chain and NADPH oxidases (NOXs). ROS would act as secondary messengers, modulating the expression of master transcription factors leading or (pre)conditioning stem cells towards differentiation. Myelodisplastic syndrome (MDS) is characterized by disturbance of the HSC differentiation and most MDS patients are treated with iron chelators to compensate for the iron overload consequent to the blood cell transfusion-based standard therapy. Intriguingly, a robust percentage of patients, treated with the iron chelator deferasirox (DFX), recover correct HSCs differentiation whereas other chelators, like deferoxamine (DFO) did not. In the presented study we investigated the effect of DFX and DFO on the redox homeostasis of hematopoietic stem/progenitor cells (HSPCs) in order to get insights on the differential effect of iron chelators in rescuing altered hematopoiesis. Materials and Methods Human HSPCs were isolated from peripheral blood (PB) or bone marrow (BM) of G-CSF-treated or untreated healthy donors, respectively, by immuno-selection against the specific markers CD133 and CD34 and resulted >99% immunophenotypically homogeneous. Mitochondrial respiratory activity was measured in intact HSPCs by high resolution oxymetry. Morpho-functional features of HSPC-mitochondria, expression of the HSPC-surface commitment markers and ROS level were analyzed by laser scanning confocal microscopy (LSCM) and flow cytometry using specific probes or antibodies. HSPCs were treated with 100 mM DFX or DFO for 24 hrs. Results Measurement of oxygen consumption rate as well as molecular analyses in PB-HSPCs confirmed a poor mitochondrial oxidative phosphorylation phenotype. LSCM imaging of mitochondria in either PB- and BM-HSCs displayed a punctuate rather than interconnected network. However, co-staining of mitochondria and CD34/CD133 stemness-markers revealed a striking inverse correlation. Finally HSPCs produced DCF-detectable and DPI-inhibitable ROS attributable to constitutive NOX activity and related to stabilization of the hypoxia-inducibile factor (HIF1a) under normoxic condition. DFX treatment of HSPCs resulted in a significant up-regulation of ROS level whereas no significant change was observed following DFO treatment. Importantly, the DFX-mediated ROS production was insensitive to treatment with low NOX-inhibiting concentration of DPI but was abrogated by high concentration of DPI thus pointing to mitochondria as ROS source. Conclusions Our results show that HSCs in the early phase of commitment undergo a progressive increase of mitochondrial mass indicating the need of a bioenergetic up-regulation to cope with the oncoming energy-demanding proliferative/differentiative phenotype. Redox signaling, mediated by ROS production and likely triggered by changes in the environmental oxygen tension, appears to be essential in regulating HSC self-renewal and preservation of pluripotency. DFX treatment, by modulating ROS production, might lead to activation of redox-sensitive key factors able to restore the hematopoietic function in MDS patients. This effect seemingly is independent on the iron-chelating property of DFX but pertains to additional pharmacological properties that warren further investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells

2019 ◽  
Vol 20 (12) ◽  
pp. 2880 ◽  
Author(s):  
Yixuan Li ◽  
Wei Zhang ◽  
Fazheng Ren ◽  
Huiyuan Guo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Bovine Lactoferrin ◽  
Osteogenic Activity ◽  
Β Receptor ◽  
Noncanonical Signaling

Lactoferrin (LF) is known to modulate the bone anabolic effect. Previously, we and others reported that the effects of LF on the bone may be conferred by the stimulation of transforming growth factor β (TGF-β) signaling in the preosteoblast. However, the underlying molecular mechanisms of LF-induced osteogenic differentiation of mesenchymal stem cells (MSCs) has not been identified. In this study, we tested the hypothesis that the effects of LF on osteogenesis of MSCs required mediation by TGF-β Receptors and activating TGF-β signaling pathway. Using siRNA silencing technology, the knockdown of TGF-β Receptor II (TβRII) could significantly attenuate LF’s effect on the proliferation rate and alkaline phosphatase (ALP) activity of MSCs. It indicated that LF induced osteogenic activity that is dependent on TβRII in C3H10T1/2. Subsequently, it was shown that LF activated Smad2. Downregulating TGF-β Receptor I (TβRI) with SB431542 attenuated the expression of p-Smad2 and p-P38, also the LF-induced the osteogenic activity. Besides, the stimulation by LF on the expression of Osteocalcin (OCN), Osteopontin (OPN), Collagen-2a1 (Col2a1), and Fibroblast Growth Factor 2 (FGF2) were abolished by SB431542. These results confirmed that LF induced osteogenic activity though the TGF-β canonical and noncanonical signaling pathway. This study provided the first evidence of the signaling mechanisms of LF’s effect on osteogenesis in MSCs.

scholarly journals Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Chenggang Zhao ◽  
Lizhu Hu ◽  
Delong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Xenograft Model ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Self Renewal

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

scholarly journals MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Development ◽  
Special Focus ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Different Cell Types

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.

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