scholarly journals Loss of Function of E-Cadherin in Embryonic Stem Cells and the Relevance to Models of Tumorigenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-19 ◽  
Author(s):  
Lisa Mohamet ◽  
Kate Hawkins ◽  
Christopher M. Ward
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Es Cells ◽  
Embryonic Stem ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Cell Metastasis ◽  
Patient Prognosis ◽  
E Cadherin

E-cadherin is the primary cell adhesion molecule within the epithelium, and loss of this protein is associated with a more aggressive tumour phenotype and poorer patient prognosis in many cancers. Loss of E-cadherin is a defining characteristic of epithelial-mesenchymal transition (EMT), a process associated with tumour cell metastasis. We have previously demonstrated an EMT event during embryonic stem (ES) cell differentiation, and that loss of E-cadherin in these cells results in altered growth factor response and changes in cell surface localisation of promigratory molecules. We discuss the implication of loss of E-cadherin in ES cells within the context of cancer stem cells and current models of tumorigenesis. We propose that aberrant E-cadherin expression is a critical contributing factor to neoplasia and the early stages of tumorigenesis in the absence of EMT by altering growth factor response of the cells, resulting in increased proliferation, decreased apoptosis, and acquisition of a stem cell-like phenotype.

323 ESTROGEN-INDUCED EPITHELIAL-MESENCHYMAL TRANSITION AND EXPRESSION OF PROAPOPTOTIC MARKERS IN PORCINE STEM CELLS

2015 ◽  
Vol 27 (1) ◽  
pp. 250
Author(s):  
Y.-S. Kim ◽  
S.-H. Hyun ◽  
C.-K. Lee ◽  
K.-C. Choi
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Steroid Hormone ◽  
Embryonic Stem ◽  
Transgenic Pig ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Apoptotic Markers ◽  
E Cadherin

In transgenic pig production for generating animal models of human diseases, apoptosis of early implantation embryo disturbs the transgenic pig production. In general, epithelial-mesenchymal transition (EMT) is considered important in embryo development and apoptosis. In addition, it was reported that 17β-oestradiol (E2), among hormones that participate in early implantation of embryo, could induce EMT and neural differentiation in mouse embryonic stem cells. Therefore, in this study, we examined the effects of the steroid hormone, E2, in the changes of EMT and apoptotic markers in porcine embryonic stem cells (pESC) and porcine induced pluripotent stem cells (piPSC). During the study, we cultured pESC and piPSC in pESC media containing basic fibroblast growth factor (b-FGF) and leukemia inhibitory factor (LIF) and performed RT-PCR and an alkaline phophatase (AP) test to measure pluripotent and undifferentiation markers of these porcine stem cells. The RT-PCR results showed that OCT4, NANOG, and SOX2 were expressed in these pESC and piPSC, indicating their pluripotency as stem cells. Also, these porcine stem cells showed positive AP activity, demonstrating undifferentiation. Additionally, we treated pESC and piPSC with E2 to examine effects of steroid hormone on the changes of EMT and apoptotic markers (i.e. bcl-2, bax, E-cad, and vimentin). The E2 treatment increased the expression of vimentin and bcl-2, while decreased the expression of E-cadherin and bax. By using immunocytochemistry (ICC), we examined the protein expression of EMT markers, which are vimentin and E-cadherin at the translational level, and found that expression of vimentin protein was increased while E-cadherin protein level was reduced at periphery of the colonies in pESC and piPSC. In conclusion, these results indicate that E2 can promote EMT process and reverse apoptosis in these pESC and iPSC. In a future study, we will further examine the effects of progesterone on the expressions of EMT and apoptotic markers in pESC and piPSC. Consequently, this study will contribute to elucidate the underlying mechanisms of EMT and apoptosis controlled by steroid hormones in porcine stem cells.

scholarly journals Polycomb Complex 2 Is Required for E-cadherin Repression by the Snail1 Transcription Factor

2008 ◽  
Vol 28 (15) ◽  
pp. 4772-4781 ◽  
Author(s):  
Nicolás Herranz ◽  
Diego Pasini ◽  
Víctor M. Díaz ◽  
Clara Francí ◽  
Arantxa Gutierrez ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Epithelial Mesenchymal Transition ◽  
Es Cells ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Cdh1 Gene ◽  
Mesenchymal Transition ◽  
Polycomb Repressive Complex 2 ◽  
Polycomb Complex ◽  
E Cadherin

ABSTRACT The transcriptional factor Snail1 is a repressor of E-cadherin (CDH1) gene expression essential for triggering epithelial-mesenchymal transition. Snail1 represses CDH1, directly binding its promoter and inducing the synthesis of the Zeb1 repressor. In this article, we show that repression of CDH1 by Snail1, but not by Zeb1, is dependent on the activity of Polycomb repressive complex 2 (PRC2). Embryonic stem (ES) cells null for Suz12, one of the components of PRC2, show higher levels of Cdh1 mRNA than control ES cells. In tumor cells, interference of PRC2 activity prevents the ability of Snail1 to downregulate CDH1 and partially derepresses CDH1. Chromatin immunoprecipitation assays demonstrated that Snail1 increases the binding of Suz12 to the CDH1 promoter and the trimethylation of lysine 27 in histone H3. Moreover, Snail1 interacts with Suz12 and Ezh2, as shown by coimmunoprecipitation experiments. In conclusion, these results demonstrate that Snail1 recruits PRC2 to the CDH1 promoter and requires the activity of this complex to repress E-cadherin expression.

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.

scholarly journals HERV-K HML-2 transcription in diverse cancers is related with cancer stem cell and epithelial-mesenchymal transition markers

2018 ◽  
Author(s):  
Audrey T. Lin ◽  
Cindy G. Santander ◽  
Fabricia F. Nascimento ◽  
Emanuele Marchi ◽  
Timokratis Karamitros ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Human Genome ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Mesenchymal Transition

AbstractEndogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the youngest lineage in the human genome, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that ERVs are transiently expressed in both stem cells and cancer, resulting in aberrant self-renewal and uncontrolled proliferation. np9 and rec expression are significantly correlated with a range of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) biomarkers, including cellular receptors, transcription factors, and histone modifiers. Surprisingly, these ERV genes are negatively correlated with genes known to promote pluripotency in embryonic stem cell lines, such as Oct4. These results indicate that HERV-K (HML-2) is part of the transcriptional landscape responsible for cancer cells undergoing the phenotypic switch that characterises EMT. The discovery of np9 and rec’s correlation with CSC and EMT biomarkers suggest a yet undescribed role affecting the transitional CSC-like state in EMT and the shift towards cancer malignancy.ImportanceIn this study, we find that human endogenous retrovirus HERV-K (HML-2)-encoded genes np9 and rec are correlated with the expression of many biomarkers associated with cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT). There has been a significant effort to develop novel treatments targeting CSC and EMT-specific signalling pathways and cell surface markers. This research describes HERV-K (HML-2) as interacting or being part of the regulatory network that make up reversible cell state switching in EMT. Our findings suggest these specific HERVs may be good candidate biomarkers in identifying the transitional CSC-like states that are present during the progression of EMT and cancer metastasis.

scholarly journals Role of the epithelial–mesenchymal transition and its effects on embryonic stem cells

2014 ◽  
Vol 46 (8) ◽  
pp. e108-e108 ◽  
Author(s):  
Ye-Seul Kim ◽  
Bo-Rim Yi ◽  
Nam-Hyung Kim ◽  
Kyung-Chul Choi
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Mesenchymal Transition

199 DIFFERENTIATION OF HIGHLY ENRICHED OLIGODENDROCYTE PRECURSORS AND MATURE OLIGODENDROCYTES FROM RHESUS MONKEY EMBRYONIC STEM CELLS

2006 ◽  
Vol 18 (2) ◽  
pp. 207
Author(s):  
T. Li ◽  
Y. Xie ◽  
W. Ji
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Rhesus Monkey ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Embryonic Stem ◽  
Oligodendrocyte Differentiation ◽  
Culture Systems ◽  
Oligodendrocyte Precursors

Generating homologous oligodendrocytes are required for studying the molecular mechanisms of oligodendrogliogenesis and for providing donor cells for transplantation therapies. Previous studies have shown that embryonic stem (ES) cells can be induced to generate neural stem cells with many kinds of culture systems; however, few or no oligodendrocytes were obtained from these culture systems. Here we present a simple method containing five steps for obtaining highly enriched oligodendrocyte precursors (75 � 6.8%) and mature oligodendrocytes (81 � 8.6%) from rhesus monkey embryonic stem (rES) cells. We expanded rES cells on a feeder layer of irradiated MESF (ear skin fibroblasts from a one-week-old rhesus monkey), formed embryoid bodies (EBs), promoted Day 9 (3 days in hanging drop and 6 days in suspension) differentiation into highly enriched (90.2 � 6.1%) neural progenitors (NPs) with hepatocyte growth factor (HGF) and G5 supplement [containing 5 ng/mL (bFGF) and 10 ng/mL epidermal growth factor (EGF)], purified NPs with 0.0625% trypsin in 0.04% EDTA (98% of cells were nestin-positive), amplified those progenitors in HGF and G5 media for two months, and then induced oligodendrocyte precursors differentiation in the absence of G5, but in the presence of 20 ng/mL HGF for 2 days. To obtain terminal oligodendrocytes, neurospheres cultured for 2 months were plated on laminin-coated plates for 3 weeks in the presence of HGF. The results showed that differentiated cells expressed myelin basic protein (MBP) and had typical mature oligodendrocyte morphology. Our studies also revealed that HGF significantly increased the NP proliferation speed (P < 0.05) by both decreasing cell apoptosis rate (P < 0.05) and shortening cell cycle time (P < 0.05) in the presence of G5. Additionally, HGF promoted oligodendrocyte maturation by increasing the length and number of branches and the expression of MBP. To test whether the original HGF had similar functions for oligodendrocyte specification, a series of experiments were evaluated by adding HGF or G5 to differentiation or expansion media at different differentiation stages. The results demonstrated that the ability of HGF responsiveness to initiate oligodendrocyte differentiation was regulated by G5 and by HGF alone without G5-induced rES cell differentiation into neurons. Further studies showed that the crucial time point of G5 action was from EBs to NPs; the early addition of HGF to EBs in the presence of G5 increased oligodendrocyte differentiation rate, but was not necessary, and the treatment during the first 2 days was enough to produce a similar effect; and HGF was required for terminal oligodendrocyte differentiation from NPs. Taken together, these results showed that HGF and G5 cooperatively promote rES cell differentiation into highly enriched oligodendrocyte precursors and mature oligodendrocytes.These observations set the method for obtaining highly enriched oligodendrocytes from ES cells in the nonhuman primate for clinical application and provide a platform to probe the molecular mechanisms that control oligodendrocyte differentiation.

scholarly journals PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhongyu Wang ◽  
Jun Shang ◽  
Zhiqin Li ◽  
Huanhuan Li ◽  
Chufan Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Biological Effects ◽  
Pi3k Pathway ◽  
Cancer Tissue ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells ◽  
Bladder Cancer Tissue ◽  
E Cadherin

PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.

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