scholarly journals Expression and Clinical Utility of Transcription Factors Involved in Epithelial–Mesenchymal Transition during Thyroid Cancer Progression

2021 ◽  
Vol 10 (18) ◽  
pp. 4076
Author(s):  
Enke Baldini ◽  
Chiara Tuccilli ◽  
Daniele Pironi ◽  
Antonio Catania ◽  
Francesco Tartaglia ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Thyroid Cancer ◽  
Cancer Progression ◽  
Clinical Utility ◽  
Epithelial Mesenchymal Transition ◽  
Clinicopathological Parameters ◽  
Mrna Levels ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
E Cadherin

The transcription factors involved in epithelial–mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients’ clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

scholarly journals Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yawei Wang ◽  
Yingying Sun ◽  
Chao Shang ◽  
Lili Chen ◽  
Hongyu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Mechanism ◽  
Regulation Mechanism ◽  
Rna Helicases ◽  
Mesenchymal Transition ◽  
Dead Box ◽  
E Cadherin

AbstractRing1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.

scholarly journals Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for Colorectal Cancer Patients with Diabetes Mellitus II

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yaodu Wang ◽  
Zhiyang Wu ◽  
Likuan Hu
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Multivariate Regression Analysis ◽  
Stage I ◽  
Clinicopathological Parameters ◽  
Mesenchymal Transition ◽  
Patients With Diabetes ◽  
E Cadherin

Objectives. We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. Methods. We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. Results. In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P=0.014) and less vimentin (P=0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P=0.048, P=0.009), tumor invasive depth (T) (P<0.001, P=0.045), and lymph invasion (N) (P=0.013, P=0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P=0.038) and metformin use (P=0.015P=0.044) and lymph invasion (P=0.016P=0.023) were considered as the prognostic factors for both DFS and overall survival (OS). Conclusion. Our study suggested that metformin may impede the EMT process and improve survival for stage I–III CRC patients with DM II.

scholarly journals Pleckstrin-2 as a Prognostic Factor and Mediator of Gastric Cancer Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jun Wang ◽  
Zhigang He ◽  
Bo Sun ◽  
Wenhai Huang ◽  
Jianbin Xiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
In Vivo Studies ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Gastric Cancer Patients

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.

SETD1A to induce epithelial-mesenchymal transition to promote invasion and metastasis through epigenetic reprogramming of snail in gastric cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 241-241
Author(s):  
Jugang Wu ◽  
Jiwei Yu ◽  
Yan Gu
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Modification ◽  
Epigenetic Reprogramming ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
E Cadherin

241 Background: Aberrant epigenetic modification induces oncogenes expression and promotes cancer development. The histone lysine methyltransferase SETD1A, which specifically methylates H3K4, is involved in tumor growth and metastasis, and its ectopic expression has been detected in aggressive malignancies. Our previous study had reported that SETD1A promoted gastric cancer (GC) proliferation and tumorigenesis. However, the function and molecular mechanisms of SETD1A in GC metastasis remain to be elucidated. Methods: Transwell migration and invasion assay were performed to determine GC cell migration and invasion. Lung metastasis assay was used to detect GC cell metastasis. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. ChIP assay was performed to investigate the methylation of H3K4. The correlation between SETD1A and EMT associated key genes in GC were performed by bioinformatic analysis. Results: In this study, we found that overexpression of SETD1A promotes GC migration and invasion, whereas knockdown of SETD1A suppressed GC migration, invasion and metastasis. Furthermore, knockdown of SETD1A suppressed GC epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin, and decreasing the expression of mesenchymal markers, including N-cadherin, Fibronectin and Vimentin. Mechanistically, knockdown of SETD1A reduced the EMT key transcriptional factors snail. SETD1A was recruited to the promoter of snail, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on snail promoter. Rescue of snail restored SETD1A knockdown-induced GC migration and invasion inhibition. In addition, linear correlation between SETD1A and several key EMT genes, including E-cadherin, Fibronectin and snail, in GC specimens obtained from TCGA dataset. Conclusions: In summary, our data reveals that SETD1A mediated EMT process and induced metastasis through epigenetic reprogramming of snail.

scholarly journals RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Danping Wang ◽  
Yifan Wang ◽  
Xuebiao Wu ◽  
Xiangxing Kong ◽  
Jun Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Colony Formation ◽  
Human Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Modification ◽  
Dependent Manner ◽  
Human Breast ◽  
Mesenchymal Transition ◽  
E Cadherin

BackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer.Experimental designWe studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses.ResultsIn this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival.ConclusionRNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer.

LncRNA CEACAMP8 Regulates the Proliferation, Invasion and Migration of Trophoblast Cells

2019 ◽  
Vol 9 (9) ◽  
pp. 1215-1221
Author(s):  
Li Jie ◽  
Zhangcai Zheng ◽  
Liping Liu ◽  
Yali Liu ◽  
Zhaoyan Meng ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Flow Cytometry Analysis ◽  
Trophoblast Cells ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Qpcr Analysis ◽  
And Migration ◽  
E Cadherin

Preeclampsia (PE) is an idiopathic hypertension syndrome occurring after 20 weeks of gestation. Reports showed that lncRNAs expression was abnormal in preeclampsia. We aimed to investigate the role of lncRNA CEACAMP8 in the proliferation, invasion and migration of trophoblast cells to improve the preeclampsia. The cell transfection effects were determined by RT-qPCR analysis. The proliferation, invasion and migration of HTR-8/SVneo cells were detected by CCK-8 assay, transwell assay and wound healing assay. The flow cytometry analysis analyzed the cell cycle. Moreover, the expression of CDK2, cyclinD1, P21, MMP2, MMP9, E-cadherin, b-catenin and vimentin was determined by the western blot analysis. Consequently, CEACAMP8 inhibition promoted the proliferation, invasion and migration of HTR-8/SVneo cells and kept most of the cells in the S phase. The expression of proteins related to the proliferation, invasion and migration of HTR-8/SVneo cells were also changed in accordance with the increase of proliferation, invasion and migration of HTR-8/SVneo cells. In addition, lncRNA CEACAMP8 inhibition decreased the expression of E-cadherin and b-catenin, and increased the vimentin expression to promote the epithelial-mesenchymal transition. And, CEACAMP8 overexpression could reverse the above changes. This study indicated that CEACAMP8 inhibition promoted the proliferation, invasion and migration of HTR-8/SVneo cells and lncRNA CEACAMP8 overexpression reversed.

scholarly journals Slug and Vimentin Downregulation at the Metastatic Site Is Associated With Skip-N2 Metastasis of Lung Adenocarcinoma

2022 ◽  
Author(s):  
Yasemin SAYGIDEGER ◽  
Alper AVCI ◽  
Emine BAGIR ◽  
Burcu SAYGIDEĞER DEMİR ◽  
Aycan SEZAN Ms ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
E Cadherin

Abstract Objective: Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. Materials and Methods: Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples.Results: Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses.Conclusion: The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.

scholarly journals Clinical significance of epithelial–mesenchymal transition–related molecules in lung adenocarcinoma

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
Y. Zhang ◽  
L. F. Wang ◽  
J. H. Gao ◽  
L. Li ◽  
P. Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumour ◽  
Smoking History ◽  
Related Protein ◽  
Vimentin Expression ◽  
Clinicopathologic Characteristics ◽  
Mesenchymal Transition ◽  
The Relationship ◽  
E Cadherin

Background Epithelial–mesenchymal transition (emt) refers to the biologic process in which epithelial cells are transformed into interstitial phenotypes by specific pathways. This transition plays an important biologic role in the process by which epithelium-derived malignant tumour cells acquire the ability to migrate and invade. We explored the relationship between emt-associated molecules and patient-related clinical factors to determine whether any clinical characteristics could be used as biomarkers for emt-related protein alterations in lung cancer—especially lung adenocarcinoma.Methods Tumour specimens were collected from 80 patients with lung adenocarcinoma who underwent surgery or lung biopsy, with 4 patients being evaluated a 2nd time after re-biopsy. Expression of emt-related proteins, including E-cadherin and vimentin, was evaluated by immunohistochemistry. We analyzed the relationship between clinicopathologic characteristics and expression level of the emt markers.Results Positive expression of E-cadherin was observed in 63 patients (79%), and vimentin, in 46 patients (57.5%). No significant relationships between E-cadherin or vimentin expression and smoking history, sex, age, driving gene mutations, or cell differentiation were identified. A significant correlation was observed between vimentin expression and pathologic stage. Of the 4 patients who were evaluated a 2nd time after re-biopsy, 3 showed the same emt-related protein expression status as in the first analysis. In the remaining patient, E-cadherin had changed completely.Conclusions Clinicopathologic factors in cancer patients did not help to diagnose emt status in lung adenocarcinoma; however, TNM stage might be associated with vimentin expression.

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