scholarly journals Cathepsin B Is Upregulated and Mediates ECM Degradation in Colon Adenocarcinoma HT29 Cells Overexpressing Snail

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 203 ◽  
Author(s):  
Jakub Kryczka ◽  
Izabela Papiewska-Pajak ◽  
M. Anna Kowalska ◽  
Joanna Boncela
Keyword(s):  
Cathepsin B ◽  
Epithelial To Mesenchymal Transition ◽  
Early Stage ◽  
Tumor Development ◽  
Colon Adenocarcinoma ◽  
Mesenchymal Cell ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Colon And Rectum ◽  
Phenotypic Shift

During tumor development and ongoing metastasis the acquisition of mesenchymal cell traits by epithelial carcinoma cells is achieved through a programmed phenotypic shift called the epithelial-to-mesenchymal transition, EMT. EMT contributes to increased cancer cell motility and invasiveness mainly through invadosomes, the adhesion structures that accompany the mesenchymal migration. The invadosomes and their associated proteases restrict protease activity to areas of the cell in direct contact with the ECM, thus precisely controlling cell invasion. Our data prove that Snail-overexpressing HT-29 cells that imitate the phenotype of colon cancer cells in the early stage of the EMT showed an increase in the expression and pericellular activity of cathepsin B. It appears that the pericellular localization of cathepsin B, also observed in colon and rectum adenocarcinoma tissue samples, plays a key role in its function.

scholarly journals Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds

2019 ◽  
Vol 20 (14) ◽  
pp. 3492 ◽  
Author(s):  
Rabiatul Adawiyah Razali ◽  
Yogeswaran Lokanathan ◽  
Muhammad Dain Yazid ◽  
Ayu Suraya Ansari ◽  
Aminuddin Bin Saim ◽  
...  
Keyword(s):  
Olea Europaea ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Healing Process ◽  
Mesenchymal Cell ◽  
Cell Phenotype ◽  
Wound Healing Process ◽  
Active Compounds ◽  
Mesenchymal Transition ◽  
Olea Europaéa

Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.

scholarly journals CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Righetti ◽  
Matteo Giulietti ◽  
Berina Šabanović ◽  
Giulia Occhipinti ◽  
Giovanni Principato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Tumor Development ◽  
Physiological Role ◽  
Mesenchymal Transition ◽  
Splicing Isoforms

CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and alters the behavior of cancer cells. Many studies investigated the roles of CXCL12 in order to understand if it has an anti- or protumor role. In particular, it seems to promote tumor invasion, proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in pancreatic cancer. Nevertheless, some evidence shows opposite functions; therefore research on CXCL12 is still ongoing. These discrepancies could be due to the presence of at least six CXCL12 splicing isoforms, each with different roles. Interestingly, three out of six variants have the highest levels of expression in the pancreas. Here, we report the current knowledge about the functions of this chemokine and then focus on pancreatic cancer. Moreover, we discuss the methods applied in recent studies in order to understand if they took into account the existence of the CXCL12 isoforms.

scholarly journals Lamins in Lung Cancer: Biomarkers and Key Factors for Disease Progression through miR-9 Regulation?

Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 78 ◽  
Author(s):  
Julien Guinde ◽  
Diane Frankel ◽  
Sophie Perrin ◽  
Valérie Delecourt ◽  
Nicolas Lévy ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Nuclear Lamina ◽  
Metastatic Potential ◽  
Disease Diagnosis ◽  
Carcinoma Cells ◽  
Scaffolding Protein ◽  
Mesenchymal Transition ◽  
Cancer Subtypes

Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve the differential diagnosis between cancer subtypes, to select the most appropriate therapy, and to establish prognostic correlations. Nuclear abnormalities are hallmarks of carcinoma cells and are used as cytological diagnostic criteria of malignancy. Lamins (divided into A- and B-types) are localized in the nuclear matrix comprising nuclear lamina, where they act as scaffolding protein, involved in many nuclear functions, with regulatory effects on the cell cycle and differentiation, senescence and apoptosis. Previous studies have suggested that lamins are involved in tumor development and progression with opposite results concerning their prognostic role. This review provides an overview of lamins expression in lung cancer and the relevance of these findings for disease diagnosis and prognosis. Furthermore, we discuss the link between A-type lamins expression in lung carcinoma cells and nuclear deformability, epithelial to mesenchymal transition, and metastatic potential, and which mechanisms could regulate A-type lamins expression in lung cancer, such as the microRNA miR-9.

Tissue Models of Peritoneal Fibrosis

2005 ◽  
Vol 28 (2) ◽  
pp. 105-111 ◽  
Author(s):  
J.A. Jiménez-Heffernan ◽  
A. Cirugeda ◽  
M.A. Bajo ◽  
G. Del Peso ◽  
M.L. Pérez-Lozano ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Epithelial To Mesenchymal Transition ◽  
Ex Vivo ◽  
Peritoneal Fibrosis ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Cellular Markers ◽  
Tissue Models ◽  
Myofibroblastic Differentiation

Objective To evaluate the utility of peritoneal pathologic samples, unrelated to peritoneal dialysis (PD) treatment, for the study of peritoneal fibrosis and inflammation. Methods Comparative morphologic and immunohistochemical study of peritoneal pathologic samples unrelated to PD with peritoneal biopsies from PD patients with special emphasis on the expression of myofibroblastic and epithelial-to-mesenchymal transition markers. Results Regarding morphology, PD-related simple fibrosis was less cellular, with greater stromal hyalinization, determining a homogeneous, hypocellular aspect of the submesothelium. In contrast, non-PD fibrosis was more cellular with an extracellular matrix showing a dense and fibrillar quality with wide bundles of collagen. Hylinazing vasculopathy was only present in PD samples. Myofibroblastic differentiation and epithelial-to-mesenchymal transition were common findings in all situations of peritoneal fibrosis. Calponin and calretinin are useful cellular markers to study such fibrogenic mechanisms and correlate with other well-known markers such as α-SMA and cytokeratins. Their expression was much more intense in those samples showing acute inflammation (peritonitis). Conclusions Non-PD models of peritoneal fibrosis seem very useful to evaluate important features of human peritoneal pathology such us fibrogenesis, and inflammation. Fibrogenic events such as myofibroblastic differentiation and epithelial-to-mesenchymal transition are evident in these tissue samples allowing us to use them as an accessible source for in vivo and ex vivo studies. Both events show their maximal expression in situations of acute inflammation supporting the important role that peritonitis episodes play in the progression of fibrosis.

Evaluation of risk recurrence in early breast cancer assessed by Oncotype DX and tumor cell dissemination to blood and bone marrow.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11516-e11516
Author(s):  
Bahriye Aktas ◽  
Agnes Bankfalvi ◽  
Martin Leonhard Heubner ◽  
Rainer Kimmig ◽  
Sabine Kasimir-Bauer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Statistical Analysis ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Data Set ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Genomic Test

e11516 Background: The OncotypeDX assay is a validated genomic test that predicts the likelihood of breast cancer (BC) recurrence, patients’ (pts) survival within 10 years of diagnosis and benefit of chemotherapy in early-stage, N0, ER-pos BC. In addition, disseminated tumor cells (DTC) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood, especially stemness like tumor cells (slCTCs) including cells being able to perform epithelial-mesenchymal transition (EMT), have been associated with worse outcome in BC. Here we use OncotypeDX as well as the presence of DTCs, CTCs and slCTCs to evaluate the risk for recurrence in early BC pts. Methods: In total, 90 pts with newly diagnosed HER2-neg early stage BC received breast conserving surgery and sentinel lymphonodectomy. 17 pts were ER-/PR-, 12 pts ER+/PR-, 3 pts ER-/PR+ and 59 pts were ER+/PR+. Analysis of OncotypeDX and KI67 were performed. In case of G2 tumors, UPA and PAI1 were determined as further proliferation markers in tissue samples. Two BM aspirates from these patients were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. Furthermore, 2 x5 ml blood were analyzed for CTCs with the AdnaTest BreastCancer for the detection of EpCAM, MUC-1, HER-2, and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for the presence of slCTCs using the AdnaTest EMT (multiplex RT-PCR for TWIST, AKT2, PI3K), and the AdnaTest TumorStemCell (ALDH1). Results: OncotypeDX was performed in 68/91 cases. 30/68 pts (44%) had a low RS, 29/68 pts (43%) an intermediate RS and 9/68 pts (13%) a high RS, respectively. BM aspiration could be performed in 70/91 pts with a positivity rate of 34% (24/70) for DTCs. CTCs were detected in 16/68 (25%) evaluable pts and slCTCs in 27/62 (44%) pts, respectively. In preliminary statistical analysis, KI67, PR and grading are showing association to RS as well as the presence of slCTCs. Tissue samples of patients with G2 tumors (N=65) underwent evaluation for UPA/PAI1analysis. Conclusions: Final statistical analysis for the complete data set including correlations to RS with all evaluable parameter will be available for presentation at the ASCO.

scholarly journals An Assessment of Epithelial and Mesenchymal Phenotypes in Experimental and Clinical Pulmonary Fibrosis

2012 ◽  
Vol 2012 ◽  
pp. 1-11
Author(s):  
Rebecca Dunmore ◽  
Alan M. Carruthers ◽  
Matthew J. Bell ◽  
Huilan Zhang ◽  
Cory M. Hogaboam ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Mesenchymal Cell ◽  
Experimental Models ◽  
Epithelial Injury ◽  
Mesenchymal Transition ◽  
Cell Markers ◽  
Apoptotic Marker ◽  
Lung Biopsies

Epithelial injury has been implicated as a driving factor for the pathogenesis of idiopathic pulmonary fibrosis (IPF). In this study we investigated changes in epithelial and mesenchymal markers in experimental models of fibrosis and associated this with IPF. TGFβ1 induced an epithelial to mesenchymal transition (EMT) phenotype in A549 cells and normal human bronchial epithelial cells, with A549 cells exhibiting a more profound transition to a mesenchymal phenotype. TGFβ1 overexpression in the lungs of mice resulted in an early increase in mesenchymal cell markers and apoptotic genes that preceded collagen deposition, suggesting an early epithelial injury triggers the downstream fibrotic response. In contrast, bleomycin had a gradual increase in mesenchymal cell marker and a decrease in E-cadherin expression that correlated with collagen protein deposition. Finally, we compared normal healthy lung tissue with surgical lung biopsies from IPF patients and observed alterations in epithelial and mesenchymal cell markers, as well as an increase in the apoptotic marker GSK3β. Interestingly, the mesenchymal changes were more profound in rapidly progressive patients in comparison to IPF patients with slowing progressing disease. In summary, this study provides evidence of alterations in epithelial and mesenchymal markers in experimental models of lung fibrosis and how these findings are relevant to clinical disease.

scholarly journals Early Development of The Trunk Neural Crest Cells in the Egyptian Cobra Naja H. Haje

2021 ◽  
Author(s):  
Eraqi R. Khannoon ◽  
Christian Alvarado ◽  
Maria Elena Elena de Bellard
Keyword(s):  
Embryonic Development ◽  
Neural Crest ◽  
Early Development ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Early Stage ◽  
Neural Crest Cells ◽  
Migratory Behavior ◽  
Mesenchymal Transition ◽  
Trunk Neural Crest

Abstract Background: Trunk neural crest cells (TNCC) are representing a model for epithelial to mesenchymal transition, this correlates the importance of studying the migration of these cells to cancer metastasis. Reptiles are unique group of animals being very morphologically diverse and their close position to synapsid leading to mammals. Recently, more publications focused on the migratory behavior of trunk NCC during embryonic development of squamates. Only one colubrid snake has been studied so far regarding the NCC migration. Results: Here we follow the migratory behavior of TNCC with HNK1 in the elapid snake Naja h. haje from early stage to 14 days postoviposition. Comparing the colubrid snake with the Egyptian cobra showed that both snakes overall follow the same TNCC migratory pathways of both birds and mammals by following the rostral and avoiding the caudal portions of the somites. Conclusions: First, TNCC intra-somitic migration as observed in turtles supports a contributing role for TNCC to scale precursors. Second, our observation of significant numbers of migrating TNCC in the intersomitic pathway suggest interesting evolutionary differences. Together, our present results of the Egyptian cobra in combination with those on a colubrid and turtle supports intersomitic TNCC as a unique reptile phenomena.

scholarly journals MicroRNA-517c Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Downregulation of KPNA2 and Inhibition of PI3K/AKT Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Limin Ma ◽  
Changming Tao ◽  
Yingying Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Analysis ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Objective. Hepatocellular carcinoma (HCC) is a kind of solid and highly aggressive malignant tumor with poor prognosis. MicroRNA (miRNA/miR) has been confirmed to be involved in HCC development. The current study focused on the functions and mechanisms of miR-517c in HCC. Methods. Expressions of miR-517c and Karyopherin α2 (KPNA2) mRNA in HCC cell lines and tissue samples were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was conducted for detections of epithelial-to-mesenchymal transition (EMT) and PI3K/AKT markers. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell assays were utilized to investigate the influence of miR-517c on HCC cell proliferation, invasion, and migration. TargetScan and luciferase reporter assay were performed to search for the potential target gene of miR-517c. Results. We demonstrated that miR-517c expressions were decreased in HCC tissues and cells. Moreover, the clinical analysis showed that decreased miR-517c expressions in HCC tissues correlated with shorter overall survival and malignant clinicopathologic features of HCC patients. MTT assay showed that miR-517c upregulation prominently repressed HCC cell proliferation. In addition, miR-517c restoration could significantly suppress HCC cell invasion and migration as demonstrated by Transwell assays. We also found that miR-517c directly targeted KPNA2 and regulated the PI3K/AKT pathway and EMT, exerting prohibitory functions in HCC. Conclusion. Taken together, this study stated that miR-517c inhibited HCC progression via regulating the PI3K/AKT pathway and EMT and targeting KPNA2 in HCC, providing a novel insight into HCC treatment.

scholarly journals Distinct Cytosine Modification Profiles Define Epithelial-to-Mesenchymal Cell-State Transitions

2021 ◽  
Author(s):  
Min Kyung Lee ◽  
Meredith S. Brown ◽  
Owen Wilkins ◽  
Diwakar R. Pattabiraman ◽  
Brock C. Christensen
Keyword(s):  
Gene Expression ◽  
Cytosine Methylation ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Cell ◽  
State Transitions ◽  
Open Chromatin ◽  
Intermediate Cell ◽  
Mesenchymal Transition ◽  
Accessible Chromatin ◽  
Cytosine Modification

Abstract Background: Epithelial-to-mesenchymal transition (EMT) is an early step in the invasion-metastasis cascade, involving progression through a number of cell intermediate states. Due to challenges with isolating intermediate cell states in EMT, genome-wide cytosine modification mechanisms that define transition through EMT states are not completely understood. We measured multiple DNA cytosine methylation modification marks, complemented with chromatin accessibility and gene expression, across clonal populations residing in specific EMT states. Results: Clones exhibiting intermediate EMT phenotypes demonstrated increased global 5-hydroxymethylcytosine (5hmC), decreased 5-methylcytosine (5mC), and more accesible chromatin. Open chromatin regions containing CpG loci with abundant 5hmC were enriched in motifs of key EMT transcription factors, ZEB1 and Snail. The magnitude of altered gene expression in intermediate cell states was higher for genes both with increased gene promoter 5hmC and differentially accessible chromatin compared with genes that exhibited differentially accessible chromatin alone, implicating functional epigenetic duality in regulation of EMT.Conclusion: Our results indicate the importance of both distinct and shared epigenetic profiles at the cytosine and chromatin level associated with EMT processes that contribute to gene regulation and which may be targeted to prevent the progression of EMT.

scholarly journals MiR-1301-3p Inhibits Epithelial to Mesenchymal Transition via Targeting RhoA in Pancreatic Cancer

2020 ◽  
Author(s):  
Xinxue Zhang ◽  
Xin Zhao ◽  
Junming Xu ◽  
Jun Ma ◽  
Zhe Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Pathological Differentiation

Abstract Background: Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC).Methods: GEO database (GSE31568, GSE41372, and GSE32688) and the PC cohort of The Cancer Genome Atlas were applied to discover the expression and prognostic role of miR-1301-3p. In the validation cohort, qRT-PCR was performed in 72 paired PC tissue samples. CCK-8, wound healing, and transwell migration assays were used to detect miR-1301-3p function on PC cells. Luciferase reporter assays and western blotting were performed to discover the potential target of miR-1301-3p on EMT.Results: Our study revealed that miR-1301-3p was downregulated in PC tissues compared with normal samples. A low level of miR-1301-3p was associated with malignant pathological differentiation, lymphatic metastasis, tumor residual, and unsatisfactory overall survival. Gene Ontology analyses indicated that miR-1301-3p possibly regulated cell cycle and adheren junction. In vitro assays showed that miR-1301-3p suppressed proliferation, migration, and invasion ability of PC cells. Mechanically, miR-1301-3p inhibits RhoA expression, and knockdown of RhoA upregulated E-cadherin; however, downregulated N-cadherin and vimentin level.Conclusions: MiR-1301-3p acts as a prognostic biomarker for PC and inhibits PC progression by targeting RhoA induced EMT process.

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