E-Cadherin Expression in Canine Melanocytic Tumors: Histological, Immunohistochemical, and Survival Analysis

E-cadherin, a glycoprotein involved in cell-cell adhesion, has a pivotal role in epithelial-mesenchymal transition, a process through which neoplastic epithelial cells develop an invasive phenotype. In human cutaneous melanomas, decreased E-cadherin expression is associated with shorter survival and increased Breslow thickness, whereas in the dog its role is poorly understood. Tumor thickness and modified Clark level were recently proposed as useful features to assess canine melanocytic tumors, but no studies investigated their association with E-cadherin expression. We performed immunohistochemistry on 77 formalin-fixed, paraffin-embedded primary canine melanocytic tumors. A 3-tier and a 2-tier classification system for assessing E-cadherin expression were tested, with the latter being more informative for the assessment of canine melanocytic tumors. E-cadherin expression was lower in cutaneous melanomas than melanocytomas, as well as in amelanotic tumors compared to pigmented tumors. In amelanotic melanomas, absent E-cadherin expression was associated with an unfavorable outcome, suggesting a potential use of this marker in defining the prognosis of amelanotic melanomas. E-cadherin expression was lower in tumors with greater tumor thickness and modified Clark level ≥IV, suggesting its possible utility in identifying the most invasive tumors. The expression of E-cadherin in oral melanomas was heterogeneous, but was associated with pigmentation and clinical outcome; thus, E-cadherin evaluation could be advantageous to detect the most aggressive neoplasms. However, cutaneous melanomas without E-cadherin expression frequently had a favorable clinical outcome. Hence, its importance as prognostic factor should be carefully considered depending on the tumor origin.

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The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-204031 ◽

2016 ◽

Vol 70 (4) ◽

pp. 331-356 ◽

Cited By ~ 10

Author(s):

Anelisa Jaca ◽

Padmini Govender ◽

Michael Locketz ◽

Richard Naidoo

Keyword(s):

Colorectal Cancer ◽

Epithelial Mesenchymal Transition ◽

Immunohistochemical Analysis ◽

Clinicopathological Features ◽

Mesenchymal Transition ◽

Expression Levels ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Sporadic Cases ◽

E Cadherin

AimsThe study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer.MethodsH&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) was performed. The miRNA-21 expression levels were determined using qRT-PCR and the data was analysed using the relative quantification method. The Fisher's exact and Pearson's χ2 tests were used to correlate snail-1, E-cadherin, miRNA-21 and clinicopathological data.ResultsOur results showed a statistically significant correlation between high miRNA-21 expression levels and E-cadherin positive cases. There was also an association between high miRNA-21 expression levels and negative snail-1 expression. No significant correlation was seen between miRNA-21 expression levels and clinicopathological features. Moreover, high expression levels of miRNA-21 were significantly associated with the sporadic cases.ConclusionsOur data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease.

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Epithelial-Mesenchymal Transition-Related MicroRNAs and Their Target Genes in Colorectal Cancerogenesis

Journal of Clinical Medicine ◽

10.3390/jcm8101603 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1603 ◽

Cited By ~ 3

Author(s):

Ranković ◽

Zidar ◽

Žlajpah ◽

Boštjančič

Keyword(s):

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Normal Mucosa ◽

Tumour Heterogeneity ◽

Mesenchymal Transition ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Zeb2 Expression ◽

Formalin Fixed ◽

E Cadherin

MicroRNAs of the miR-200 family have been shown experimentally to regulate epithelial-mesenchymal transition (EMT). Although EMT is the postulated mechanism of development and progression of colorectal cancer (CRC), there are still limited and controversial data on expression of miR-200 family and their target genes during CRC cancerogenesis. Our study included formalin-fixed paraffin-embedded biopsy samples of 40 patients (10 adenomas and 30 cases of CRC with corresponding normal mucosa). Expression of miR-141, miR-200a/b/c and miR-429 and their target genes (CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2) was analysed using quantitative real-time PCR. Expression of E-cadherin was analysed using immunohistochemistry. All miRNAs were down-regulated and their target genes showed the opposite expression in CRC compared to adenoma. Down-regulation of the miR-200 family at the invasive front in comparison to the central part of tumour was observed as well as a correlation of expression of miR-200b, CDKN1B, ONECUT2 and ZEB2 expression to nodal metastases. Expression of the miR-200 family and SOX2 also correlated with E-cadherin staining. These results suggest that the miR-200 family and their target genes contribute to progression of adenoma to CRC, invasive properties and development of metastases. Our results strongly support the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRC cancerogenesis.

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NOTCH3 limits the epithelial–mesenchymal transition and predicts a favorable clinical outcome in esophageal cancer

Cancer Medicine ◽

10.1002/cam4.3933 ◽

2021 ◽

Author(s):

Norihiro Matsuura ◽

Koji Tanaka ◽

Makoto Yamasaki ◽

Kotaro Yamashita ◽

Takuro Saito ◽

...

Keyword(s):

Esophageal Cancer ◽

Clinical Outcome ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Favorable Clinical Outcome

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The Association of Extravasated Platelet Aggregation With Clinical Futures in Patients With Colorectal Cancer and Its Correlation With EMT Markers

ACTA MEDICA IRANICA ◽

10.18502/acta.v58i6.4052 ◽

2020 ◽

Author(s):

Naghmeh Ahmadiankia ◽

Maryam Yarmohammadi ◽

Azam Hadi ◽

Behnaz Jafari ◽

Mozhgan Fazli ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Patient Characteristics ◽

Specific Marker ◽

Mesenchymal Transition ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Emt Markers ◽

Formalin Fixed

The theory of platelet role in cancer progression was recently introduced. We investigated the association of extravasated platelets in colorectal cancer with clinicopathological features, and also the expression of epithelial-mesenchymal transition (EMT) markers. We retrospectively analyzed data from 33 patients with colorectal cancer who underwent surgery between 2013-2016. In formalin-fixed paraffin-embedded tissues, we evaluated the expression of a platelet-specific marker of CD42b and EMT markers using immunohistochemistry. The associations among the expression of the platelet‑specific marker in specimens, EMT, and clinicopathological futures were analyzed. The presence of platelets was observed in 15 out of 33 primary colorectal tumors (45%). According to multivariate analysis, CD42b expression was not correlated with clinical characteristics. Platelet-positive tumor cells did not show EMT marker expression. These data suggest that extravasated platelets may not have a central role in determining patient characteristics and clinical futures.

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ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial–mesenchymal transition

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01540-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kejun Liu ◽

Xianwen Chen ◽

Ligang Wu ◽

Shiyuan Chen ◽

Nianxin Fang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Small Cell Lung Cancer ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Egfr T790m ◽

E Cadherin

Abstract Background ID1 is associated with resistance to the first generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, the effect of ID1 expression on osimertinib resistance in EGFR T790M-positive NSCLC is not clear. Methods We established a drug-resistant cell line, H1975/OR, from the osimertinib-sensitive cell line H1975. Alterations in ID1 protein expression and Epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA levels. ID1 silencing and overexpression were used to investigate the effects of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess the proliferation rate in cells with altered of ID1 expression. Transwell assay was used to evaluate the invasion ability of different cells. The effects on the cell cycle and apoptosis were also compared using flow cytometry. Results In our study, we found that in osimertinib-resistant NSCLC cells, the expression level of the EMT-related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin were higher than those of sensitive cells. ID1 expression levels was closely related to E-cadherin and vimentin in both osimertinib-sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression in H1975/OR cells could inhibit cell proliferation, reduce cell invasion, promote cell apoptosis and arrested the cell cycle in the G1/G0 stage phase. Our study suggests that ID1 may induce EMT in EGFR T790M-positive NSCLC, which mediates drug resistance of osimertinib. Conclusions Our study revealed the mechanism of ID1 mediated resistance to osimertinib in EGFR T790M-positive NSCLC through EMT, which may provide new ideas and methods for the treatment of EGFR mutated NSCLC after osimertinib resistance.

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

Cell Death and Disease ◽

10.1038/s41419-021-03491-4 ◽

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.

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Absence of EpCAM in cervical cancer cells is involved in slug induced epithelial-mesenchymal transition

Cancer Cell International ◽

10.1186/s12935-021-01858-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xian Liu ◽

Qian Feng ◽

Yanru Zhang ◽

PengSheng Zheng ◽

Nan Cui

Keyword(s):

Cervical Cancer ◽

Cell Motility ◽

Cancer Cells ◽

Negative Correlation ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Suppression Effect ◽

Epcam Expression ◽

Cervical Cancer Cells ◽

E Cadherin

Abstract Background Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study. Methods RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation. Results Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis. Conclusions These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin.

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

Gastroenterology Research and Practice ◽

10.1155/2017/2520581 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 5

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.

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The Impacts of Bone Marrow Mesenchymal Stem Cells (BMSCs)-Derived Periostin on Epithelial-Mesenchymal Transition (EMT) of Cervical Cancer Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2958 ◽

2022 ◽

Vol 12 (4) ◽

pp. 820-826

Author(s):

Chengyong Wu ◽

Weifeng Wei ◽

Jing Li ◽

Shenglin Peng

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Signal Transduction Pathway ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Essential Components ◽

Cervical Cancer Cells ◽

E Cadherin

Epithelial-mesenchymal transition (EMT) is closely related to the migrating and invading behaviors of cells. Periostin is one of the essential components in the extracellular matrix and can induce EMT of cells and their sequential metastasis. But its underlying mechanism is unclear. The Hela and BMSC cell lines were assigned into Periostin-mimic group, Periostin-Inhibitor group and Periostin-NC group followed by analysis of cell migration and invasion, expression of E-Cadherin, Vimentin, β-Catenin, Snail, MMP-2, MMP-9, PTEN, and p-PTEN. Cells in Periostin-mimic group exhibited lowest migration, least number of invaded cells, as well as lowest levels of Vimentin, β-Catenin, Snail, MMP-2, MMP-9, p-PTEN, Akt, p-Akt, p-GSK-3β, p-PDK1 and p-cRcf, along with highest levels of E-cadherin and PTEN. Moreover, cells in Periostin-NC group had intermediate levels of these above indicators, while, the Periostin-Inhibitor group exhibited the highest migration rate, the most number of invaded cells, and the highest levels of these proteins (P < 0.05). In conclusion, BMSCs-derived Periostin can influence the EMT of cervical cancer cells possibly through restraining the activity of the PI3K/AKT signal transduction pathway, indicating that Periostin might be a target of chemotherapy in clinics for the treatment of cervical cancer.

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