scholarly journals ANALYSIS OF E-CADHERIN EXPRESSION IN A GROUP OF PRIMARY CUTANEOUS SQUAMOUS CELL CARCINOMAS

2019 ◽  
Vol 2 (2) ◽  
Author(s):  
Andreea Calinescu ◽  
Cristian Scheau ◽  
Sabina Zurac ◽  
Roxana Ioana Nedelcu ◽  
Alice Brinzea ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Squamous Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Squamous Cell Carcinomas ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Invasion Front ◽  
Knowing That ◽  
Tumoral Cells ◽  
E Cadherin

E-cadherin is an adhesion molecule essential in maintaining cellular integrity and preserving normal epithelial tissue architecture in adult organisms. Loss of E-cadherin expression and epithelial characteristics has been described in the late stages of carcinogenesis in various human cancers. By loosing cell-cell adhesion mediated by E-cadherin and acquiring mesenchymal properties, a process reffered to as epithelial to mesenchymal transition (EMT), carcinoma cells become more motile and invasive, thus being able to penetrate the surrounding stroma. Our aim is to investigate E-cadherin expression, part of the EMT phenomenom, in cutaneous squamous cell carcinomas (cSCCs), knowing that it represents a valuable model for understanding cancer progression. We conducted a retrospective study, performing immunohistochemical staining of E-cadherin and analyzing its expression in 32 cases of primary cSCCs. E-cadherin membrane positivity was assessed in cells from the main tumor and cells from the invasion front and described in terms of percentage of positive tumoral cells and in terms of intensity. Statistycal analysis showed the proportion of E-Cadherin positive cells in the tumor central and superficial areas is lower in higher degrees of anaplasia (marginally significant p=0.07), confirming the higher potential of poor outcome in these tumors. Median intensity and proportion values of E-Cadherin positive cells were significantly higher in the tumor central and superficial areas than in the invasion front (p<0.0001), suggesting that loss of epithelial features portends higher potential of invasion and metastasis in the setting of EMT. Further studies are required in order to establish clear correlations.

scholarly journals The Autophagic Route of E-Cadherin and Cell Adhesion Molecules in Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6328
Author(s):  
Manuela Santarosa ◽  
Roberta Maestro
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cancer Progression ◽  
Cell Adhesion Molecules ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Transformation ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Intracellular Degradation ◽  
E Cadherin

Cell-to-cell adhesion is a key element in epithelial tissue integrity and homeostasis during embryogenesis, response to damage, and differentiation. Loss of cell adhesion and gain of mesenchymal features, a phenomenon known as epithelial to mesenchymal transition (EMT), are essential steps in cancer progression. Interestingly, downregulation or degradation by endocytosis of epithelial adhesion molecules (e.g., E-cadherin) associates with EMT and promotes cell migration. Autophagy is a physiological intracellular degradation and recycling process. In cancer, it is thought to exert a tumor suppressive role in the early phases of cell transformation but, once cells have gained a fully transformed phenotype, autophagy may fuel malignant progression by promoting EMT and conferring drug resistance. In this review, we discuss the crosstalk between autophagy, EMT, and turnover of epithelial cell adhesion molecules, with particular attention to E-cadherin.

scholarly journals Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade

2021 ◽  
Vol 22 (6) ◽  
pp. 2844
Author(s):  
Alena Mickova ◽  
Gvantsa Kharaishvili ◽  
Daniela Kurfurstova ◽  
Mariam Gachechiladze ◽  
Milan Kral ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Therapy Resistance ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
Chemical Inhibition ◽  
Novel Treatment Strategies ◽  
E Cadherin

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors.

scholarly journals Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial–Mesenchymal Transition

2021 ◽  
Vol 11 ◽  
Author(s):  
Boli Yang ◽  
Qiuyu Chen ◽  
Changshan Wan ◽  
Siyuan Sun ◽  
Lanping Zhu ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Squamous Cell Carcinomas ◽  
Malignant Progression ◽  
Expression Level ◽  
Migration And Invasion ◽  
Control Group ◽  
Mesenchymal Transition ◽  
Esophageal Squamous Cell Carcinomas ◽  
E Cadherin

ObjectiveThis article investigates the role of Transgelin (TAGLN) in the epithelial–mesenchymal transition (EMT) of esophageal squamous cell carcinomas (ESCC) and its possible mechanism of inhibiting the invasion of these cancers.MethodsTissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between Transgelin expression level and prognosis of patients with ESCC. Transgelin siRNA was used to knock down Transgelin expression. The expression of Transgelin in Eca-109 and KYSE-150 cells was overexpressed by Transgelin-overexpressing plasmid. The effects of Transgelin overexpression and knockdown on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, and CCK-8 cell activity assay. RT-PCR and Western blot were used to detect the effect of Transgelin overexpression or knockdown on the mRNA and protein expressions of E-cadherin and Vimentin. TCGA data were used to analyze Transgelin co-expressed genes and further study the GO and KEGG enrichment analysis results under the influence of Transgelin.ResultsThe expression of Transgelin was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The targeted Transgelin siRNA and Transgelin-overexpressing plasmid can effectively regulate the expression of Transgelin mRNA and protein in Eca-109 and KYSE-150 cells. After overexpression of Transgelin, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells were significantly decreased compared with those of the control group (P &lt; 0.05). However, Transgelin knockdown could promote the proliferation, migration, and invasion of ESCC cells. The overexpression of Transgelin inhibits EMT in ESCC. With the increase of Transgelin expression in Eca-109 and KYSE-150 cells, the expression of E-cadherin increased, while the expression of Vimentin decreased, and the difference was statistically significant (P &lt; 0.05).ConclusionTransgelin can inhibit the malignant progression of ESCC by inhibiting the occurrence of EMT.

scholarly journals Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event

2019 ◽  
Vol 20 (1) ◽  
pp. 150 ◽  
Author(s):  
Stefano Turini ◽  
Loredana Bergandi ◽  
Elena Gazzano ◽  
Mauro Prato ◽  
Elisabetta Aldieri
Keyword(s):  
Zinc Finger ◽  
Cancer Progression ◽  
Malignant Mesothelioma ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Zinc Finger Protein ◽  
Asbestos Exposure ◽  
Mesothelial Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Asbestos exposure increases the risk of asbestosis and malignant mesothelioma (MM). Both fibrosis and cancer have been correlated with the Epithelial to Mesenchymal Transition (EMT)—an event involved in fibrotic development and cancer progression. During EMT, epithelial cells acquire a mesenchymal phenotype by modulating some proteins. Different factors can induce EMT, but Transforming Growth Factor β (TGF-β) plays a crucial role in promoting EMT. In this work, we verified if EMT could be associated with MM development. We explored EMT in human mesothelial cells (MeT-5A) exposed to chrysotile asbestos: we demonstrated that asbestos induces EMT in MeT-5A cells by downregulating epithelial markers E-cadherin, β-catenin, and occludin, and contemporarily, by upregulating mesenchymal markers fibronectin, α-SMA, and vimentin, thus promoting EMT. In these cells, this mechanism is mediated by increased TGF-β secretion, which in turn downregulates E-cadherin and increases fibronectin. These events are reverted in the presence of TGF-β antibody, via a Small Mother Against Decapentaplegic (SMAD)-dependent pathway and its downstream effectors, such as Zinc finger protein SNAI1 (SNAIL-1), Twist-related protein (Twist), and Zinc Finger E-Box Binding Homeobox 1 (ZEB-1), which downregulate the E-cadherin gene. Since SNAIL-1, Twist, and ZEB-1 have been shown to be overexpressed in MM, these genes could be considered possible predictive or diagnostic markers of MM development.

scholarly journals N-Cadherin Extracellular Repeat 4 Mediates Epithelial to Mesenchymal Transition and Increased Motility

2000 ◽  
Vol 151 (6) ◽  
pp. 1193-1206 ◽  
Author(s):  
Jae-Beom Kim ◽  
Shahidul Islam ◽  
Young J. Kim ◽  
Ryan S. Prudoff ◽  
Kristin M. Sass ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Motility ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Cellular Behavior ◽  
Cellular Behaviors ◽  
Necessary And Sufficient ◽  
Inappropriate Expression ◽  
E Cadherin

E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69–amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.

scholarly journals Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas

2021 ◽  
Vol 22 (19) ◽  
pp. 10588
Author(s):  
Federico Armando ◽  
Samanta Mecocci ◽  
Virginia Orlandi ◽  
Ilaria Porcellato ◽  
Katia Cappelli ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Squamous Cell Carcinomas ◽  
Pcr Analysis ◽  
Mesenchymal Transition ◽  
Pathway Activation ◽  
Twist 1 ◽  
Penile Squamous Cell Carcinoma ◽  
Canonical Wnt

Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of RANKL, together with BCATN1, LEF1, and FOSL1 genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas

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