scholarly journals Expression of the microRNA-200 Family, microRNA-205, and Markers of Epithelial–Mesenchymal Transition as Predictors for Endoscopic Submucosal Dissection over Esophagectomy in Esophageal Adenocarcinoma: A Single-Center Experience

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 486
Author(s):  
Daniel Neureiter ◽  
Christian Mayr ◽  
Paul Winkelmann ◽  
Bettina Neumayer ◽  
Eckhard Klieser ◽  
...  
Keyword(s):  
Endoscopic Submucosal Dissection ◽  
Clinical Evaluation ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Level ◽  
Expression Profiles ◽  
High Expression ◽  
Protein Markers ◽  
Discrimination Power ◽  
Mesenchymal Transition ◽  
Submucosal Dissection

Endoscopic submucosal dissection (ESD) is an effective treatment of early esophageal adenocarcinomas (EACs). The decision of ESD over esophagectomy is based on clinical evaluation of tumor depth and invasion. On a molecular level, tumor invasion is strongly associated with epithelial-to-mesenchymal transition (EMT). Here, we investigated whether localized ESD-resected and surgically resected EAC samples displayed different expression profiles of EMT protein and microRNA markers and whether these different expression profiles were able to retrospectively discriminate localized and surgically resected samples. By doing this, we aimed to evaluate whether preoperative measurement of EMT marker expression might support the decision regarding ESD over surgery. The results showed that ESD-resected samples displayed an epithelial expression profile, i.e., high expression of epithelial protein markers, whereas surgically resected samples displayed high expression of mesenchymal markers. In addition, the anti-EMT microRNA-205 was significantly more expressed in ESD-resected samples, whereas we found no significant differences in the expression levels of microRNA-200 family members. Furthermore, in our retrospective approach, we have demonstrated that measurement of selected EMT markers and microRNA-205 has significant discrimination power to distinguish ESD-resected and surgically resected samples. We suggest that the assessment of EMT status of EAC samples on a molecular level may support clinical evaluation regarding the applicability of ESD.

scholarly journals Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Dismal Prognosis ◽  
Advanced Tumor

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

scholarly journals AKT3 Expression in Mesenchymal Colorectal Cancer Cells Drives Growth and Is Associated with Epithelial-Mesenchymal Transition

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 801
Author(s):  
Joyce Y. Buikhuisen ◽  
Patricia M. Gomez Barila ◽  
Arezo Torang ◽  
Daniëlle Dekker ◽  
Joan H. de Jong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Surrogate Marker ◽  
High Expression ◽  
Mesenchymal Transition ◽  
High Propensity ◽  
Colorectal Cancer Cells ◽  
Epithelial Compartment ◽  
Selection Of

Colorectal cancer (CRC) is a heterogeneous disease that can currently be subdivided into four distinct consensus molecular subtypes (CMS) based on gene expression profiling. The CMS4 subtype is marked by high expression of mesenchymal genes and is associated with a worse overall prognosis compared to other CMSs. Importantly, this subtype responds poorly to the standard therapies currently used to treat CRC. We set out to explore what regulatory signalling networks underlie the CMS4 phenotype of cancer cells, specifically, by analysing which kinases were more highly expressed in this subtype compared to others. We found AKT3 to be expressed in the cancer cell epithelium of CRC specimens, patient derived xenograft (PDX) models and in (primary) cell cultures representing CMS4. Importantly, chemical inhibition or knockout of this gene hampers outgrowth of this subtype, as AKT3 controls expression of the cell cycle regulator p27KIP1. Furthermore, high AKT3 expression was associated with high expression of epithelial-mesenchymal transition (EMT) genes, and this observation could be expanded to cell lines representing other carcinoma types. More importantly, this association allowed for the identification of CRC patients with a high propensity to metastasise and an associated poor prognosis. High AKT3 expression in the tumour epithelial compartment may thus be used as a surrogate marker for EMT and may allow for a selection of CRC patients that could benefit from AKT3-targeted therapy.

High-Expression of Neuropilin 1 Correlates to Estrogen-Induced Epithelial-Mesenchymal Transition of Endometrial Cells in Adenomyosis

2020 ◽  
Vol 27 (1) ◽  
pp. 395-403 ◽  
Author(s):  
Rong Hu ◽  
Guo-Qing Peng ◽  
De-Ying Ban ◽  
Chun Zhang ◽  
Xiao-Qiong Zhang ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mesenchymal Transition ◽  
Endometrial Cells ◽  
Neuropilin 1

scholarly journals P11.16 The stemness andinvasiveness of glioblastoma tumorspheres were suppressed by combined treatment with2’-hydroxycinnamaldehyde andtemozolomide

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii45-iii46
Author(s):  
W Kim
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Expression Profiles ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Orthotopic Xenograft ◽  
Orthotopic Xenograft Model

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive human primary brain malignancy. The key properties of GBM, stemness and invasiveness, are known to be associated with a highly unfavorable prognosis. Notably, the process of epithelial-mesenchymal transition (EMT) is closely related to the progression of GBM. On the basis of reports that 2′-hydroxycinnamaldehyde (HCA) and its derivative, 2′-benzoyloxycinnamaldehyde (BCA), suppresses EMT in several human cancer cells, we sought to evaluate the therapeutic efficacy of HCA and BCA, alone and in combination with temozolomide (TMZ), on GBM tumorspheres (TSs). MATERIAL AND METHODS Two human GBM TSs were treated with HCA, BCA, or TMZ. Therapeutic effects were evaluated by measuring ATP levels, neurosphere formation, 3D-invasion in collagen matrix, and viability. Protein expression profiles after drug treatment were evaluated by western blotting. In vivo anticancer efficacy of drugs was examined in a mouse orthotopic xenograft model. RESULTS Combined treatment of GBM TSs with HCA or BCA and TMZ significantly reduced cell viability, stemness, and invasiveness. Expression levels of stemness-, invasiveness-, and mesenchymal transition-associated markers, Zeb1, N-cadherin, and β-catenin, were also substantially decreased by the combined treatment. The combined treatment also reduced tumor growth in a mouse orthotopic xenograft model. CONCLUSION Our findings suggest that HCA and BCA, combined with TMZ, are potential therapeutic agents in the treatment of GBM.

Sarcomatoid renal cell carcinoma is an example of epithelial–mesenchymal transition

2011 ◽  
Vol 64 (12) ◽  
pp. 1088-1092 ◽  
Author(s):  
Joanna L Conant ◽  
Zhihua Peng ◽  
Mark F Evans ◽  
Shelly Naud ◽  
Kumarasen Cooper
Keyword(s):  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Phenotypic Expression ◽  
High Expression ◽  
Rank Test ◽  
Mesenchymal Transition ◽  
Signed Rank ◽  
Signed Rank Test ◽  
Sarcomatoid Renal Cell Carcinoma ◽  
E Cadherin

BackgroundSarcomatoid renal cell carcinomas (SRCC) are composed of two cell populations, a sarcomatous component (SC) and a carcinomatous component (CC). SRCC are particularly aggressive and often present at an advanced stage at diagnosis. Epithelial–mesenchymal transition (EMT) has been proposed as a mechanism for the development of SC from CC.Aims and methodsE- to N-cadherin switching, localisation of β-catenin, and expression of Snail and secreted protein acidic and rich in cysteine (SPARC) (markers of EMT) were studied to determine whether SRCC is an example of EMT. Expression of these markers was analysed by immunohistochemistry on 21 cases of SRCC that had both SC and CC and scored according to intensity and extent.ResultsE-cadherin expression was decreased in SC (Wilcoxon signed-rank test, p=0.0004) while N-cadherin expression was high in both components (p=0.46). Membranous β-catenin expression was decreased in SC (p<0.0001) while cytoplasmic expression was increased (p=0.0002). Snail and SPARC had higher expression in SC (p=0.002 and p<0.0001, respectively). When the scores were dichotomised into low and high expression levels, the results using McNemar's test substantiated the above results.ConclusionsE- to N-cadherin switching, dissociation of β-catenin from the membrane, and increased expression of Snail and SPARC in SC indicate that SRCC is an example of EMT. High expression of N-cadherin and Snail in CC suggest early involvement in initiating EMT. Once EMT is established, loss of E-cadherin, release of β-catenin into the cytoplasm, and expression of SPARC correspond with mesenchymal phenotypic expression.

High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells

2011 ◽  
Vol 310 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Chihiro Yokomizo ◽  
Kanji Yamaguchi ◽  
Yoshito Itoh ◽  
Takeshi Nishimura ◽  
Atsushi Umemura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mesenchymal Transition ◽  
Hcc Cells

scholarly journals The Early Pregnancy Human Placenta Shares Hypomethylation Patterns Characteristic of Solid Tumors

2017 ◽  
Author(s):  
Akpéli V. Nordor ◽  
Djamel Nehar-Belaid ◽  
Sophie Richon ◽  
David Klatzmann ◽  
Dominique Bellet ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Drug Targets ◽  
Large Scale ◽  
Epithelial Mesenchymal Transition ◽  
Time Window ◽  
Expression Profiles ◽  
Colon Adenocarcinoma ◽  
First Trimester ◽  
Maternal Blood ◽  
Mesenchymal Transition

ABSTRACTBackgroundThe placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis, while surviving hypoxia, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors.ResultsWe show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition (EMT), immune response and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B (NF-kB) is a key hub.ConclusionTaken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.

scholarly journals Addiction of mesenchymal phenotypes on the FGF/FGFR axis in oral squamous cell carcinoma cells

2019 ◽  
Author(s):  
Asami Hotta Osada ◽  
Kaori Endo ◽  
Yujiro Kimura ◽  
Kei Sakamoto ◽  
Ryosuke Nakamura ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Constitutive Expression ◽  
Fibroblast Growth Factor Receptors ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness

AbstractThe epithelial–mesenchymal transition (EMT) is a crucial morphological event that occurs during epithelial tumor progression. ZEB1/2 are EMT transcription factors that are positively correlated with EMT phenotypes and breast cancer aggressiveness. ZEB1/2 regulate the alternative splicing and hence isoform switching of fibroblast growth factor receptors (FGFRs) by repressing the epithelial splicing regulatory proteins, ESRP1 and ESRP2. Here, we show that the mesenchymal-like phenotypes of oral squamous cell carcinoma (OSCC) cells are dependent on autocrine FGF–FGFR signaling. Mesenchymal-like OSCC cells express low levels of ESRP1/2 and high levels of ZEB1/2, resulting in constitutive expression of the IIIc-isoform of FGFR, FGFR(IIIc). By contrast, epithelial-like OSCC cells showed opposite expression profiles for these proteins and constitutive expression of the IIIb-isoform of FGFR2, FGFR2(IIIb). Importantly, ERK was constitutively phosphorylated through FGFR1(IIIc), which was activated by factors secreted autonomously by mesenchymal-like OSCC cells and involved in sustained high-level expression of ZEB1. Antagonizing FGFR1 with either an inhibitor or siRNAs considerably repressed ZEB1 expression and restored epithelial-like traits. Therefore, autocrine FGF–FGFR(IIIc) signaling appears to be responsible for sustaining ZEB1/2 at high levels and the EMT phenotype in OSCC cells.

scholarly journals Discovery and Validation of an Epithelial-Mesenchymal Transition-Based Signature in Gastric Cancer by Genomics and Prognosis Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-35
Author(s):  
Huiyong Xu ◽  
Huilai Wan ◽  
Maoshu Zhu ◽  
Lianghua Feng ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Cell Cancer ◽  
External Validation ◽  
Receptor Interaction ◽  
Related Gene ◽  
Mesenchymal Transition

Objective. Epithelial-mesenchymal transition (EMT) exerts a key function in cancer initiation and progression. Herein, we aimed to develop an EMT-based prognostic signature in gastric cancer. Methods. The gene expression profiles of gastric cancer were obtained from TCGA dataset as a training set and GSE66229 and GSE84437 datasets as validation sets. By LASSO regression and Cox regression analyses, key prognostic EMT-related genes were screened for developing a risk score (RS) model. Potential small molecular compounds were predicted by the CMap database based on the RS model. GSEA was employed to explore signaling pathways associated with the RS. ESTIMATE and seven algorithms (TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC) were applied to assess the RS and immune microenvironment. Results. This study developed an EMT-related gene signature comprised of SERPINE1, PCOLCE2, MATN3, and DKK1. High-RS patients displayed poorer survival outcomes than those with low RS. ROC curves demonstrated the robustness of the model in predicting the prognosis. After external validation, the RS model was an independent risk factor for gastric cancer. Several compounds were predicted for gastric cancer treatment based on the RS model. ECM receptor interaction, focal adhesion, pathway in cancer, TGF-beta, and WNT pathways were distinctly activated in high-RS samples. Also, high RS was significantly associated with increased stromal and immune scores and increased infiltration of CD4+ T cell, CD8+ T cell, cancer-associated fibroblast, and macrophage in gastric cancer tissues. Conclusion. Our findings suggested that the EMT-related gene model may robustly predict gastric cancer prognosis, which could improve the efficacy of personalized therapy.

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