scholarly journals Cadherin Expression and EMT: A Focus on Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1328
Author(s):  
Carolina Noronha ◽  
Ana Sofia Ribeiro ◽  
Ricardo Taipa ◽  
Diogo S. Castro ◽  
Joaquim Reis ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Calcium Binding ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Potential Contribution ◽  
Epithelial Tumor ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Tumor Invasiveness ◽  
Cell Adhesion And Migration

Cadherins are calcium-binding proteins with a pivotal role in cell adhesion and tissue homeostasis. The cadherin-dependent mechanisms of cell adhesion and migration are exploited by cancer cells, contributing to tumor invasiveness and dissemination. In particular, cadherin switch is a hallmark of epithelial to mesenchymal transition, a complex development process vastly described in the progression of most epithelial cancers. This is characterized by drastic changes in cell polarity, adhesion, and motility, which lead from an E-cadherin positive differentiated epithelial state into a dedifferentiated mesenchymal-like state, prone to metastization and defined by N-cadherin expression. Although vastly explored in epithelial cancers, how these mechanisms contribute to the pathogenesis of other non-epithelial tumor types is poorly understood. Herein, the current knowledge on cadherin expression in normal development in parallel to tumor pathogenesis is reviewed, focusing on epithelial to mesenchymal transition. Emphasis is taken in the unascertained cadherin expression in CNS tumors, particularly in gliomas, where the potential contribution of an epithelial-to-mesenchymal-like process to glioma genesis and how this may be associated with changes in cadherin expression is discussed.

scholarly journals TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in Glioblastoma multiforme

2021 ◽  
Author(s):  
Lee Admoni-Elisha ◽  
Michal Feldman ◽  
Tzofit Elbaz ◽  
Anand Chopra ◽  
Guy Shapira ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Glioblastoma Multiforme ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Helix Loop Helix ◽  
Non Coding Rna ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Repressive H3k27me3 Mark

Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor among adults, which is characterized by high invasion, migration and proliferation abilities. One important process that contributes to the invasiveness of GBM is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in GBM patients. RNA-seq analysis in U251 GBM cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby suppressing EMT in GBM. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.

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 Adhesion Deregulation in Acute Myeloid Leukaemia

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 66 ◽  
Author(s):  
Alicja Gruszka ◽  
Debora Valli ◽  
Cecilia Restelli ◽  
Myriam Alcalay
Keyword(s):  
Cell Adhesion ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Epithelial To Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Prognostic Impact ◽  
Mesenchymal Transition ◽  
Haematopoietic Cells ◽  
Variable Extent ◽  
Acute Myeloid

Cell adhesion is a process through which cells interact with and attach to neighboring cells or matrix using specialized surface cell adhesion molecules (AMs). Adhesion plays an important role in normal haematopoiesis and in acute myeloid leukaemia (AML). AML blasts express many of the AMs identified on normal haematopoietic precursors. Differential expression of AMs between normal haematopoietic cells and leukaemic blasts has been documented to a variable extent, likely reflecting the heterogeneity of the disease. AMs govern a variety of processes within the bone marrow (BM), such as migration, homing, and quiescence. AML blasts home to the BM, as the AM-mediated interaction with the niche protects them from chemotherapeutic agents. On the contrary, they detach from the niches and move from the BM into the peripheral blood to colonize other sites, i.e., the spleen and liver, possibly in a process that is reminiscent of epithelial-to-mesenchymal-transition in metastatic solid cancers. The expression of AMs has a prognostic impact and there are ongoing efforts to therapeutically target adhesion in the fight against leukaemia.

scholarly journals Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells

2019 ◽  
Vol 8 (5) ◽  
pp. 642 ◽  
Author(s):  
Snahlata Singh ◽  
Rumela Chakrabarti
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Response ◽  
Current Knowledge ◽  
Cell Contact ◽  
Invasive Potential ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

Epithelial-to-mesenchymal transition (EMT) is a process through which epithelial cells lose their epithelial characteristics and cell–cell contact, thus increasing their invasive potential. In addition to its well-known roles in embryonic development, wound healing, and regeneration, EMT plays an important role in tumor progression and metastatic invasion. In breast cancer, EMT both increases the migratory capacity and invasive potential of tumor cells, and initiates protumorigenic alterations in the tumor microenvironment (TME). In particular, recent evidence has linked increased expression of EMT markers such as TWIST1 and MMPs in breast tumors with increased immune infiltration in the TME. These immune cells then provide cues that promote immune evasion by tumor cells, which is associated with enhanced tumor progression and metastasis. In the current review, we will summarize the current knowledge of the role of EMT in the biology of different subtypes of breast cancer. We will further explore the correlation between genetic switches leading to EMT and EMT-induced alterations within the TME that drive tumor growth and metastasis, as well as their possible effect on therapeutic response in breast cancer.

scholarly journals Two Faces of TGF-Beta1 in Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Joanna Magdalena Zarzynska
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Clinical Investigation ◽  
Mesenchymal Transition ◽  
Early Stages ◽  
New Therapeutic Approaches ◽  
Genes Encoding ◽  
Life Threatening

Breast cancer (BC) is potentially life-threatening malignancy that still causes high mortality among women. Scientific research in this field is focused on deeper understanding of pathogenesis and progressing of BC, in order to develop relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine TGF-β1 is one of many factors that have a direct influence on BC pathophysiology. Expression of TGF-β1, induction of canonical and noncanonical signaling pathways, and mutations in genes encoding TGF-β1 and its receptors are correlated with oncogenic activity of this cytokine. In early stages of BC this cytokine inhibits epithelial cell cycle progression and promotes apoptosis, showing tumor suppressive effects. However, in late stages, TGF-β1 is linked with increased tumor progression, higher cell motility, cancer invasiveness, and metastasis. It is also involved in cancer microenvironment modification and promotion of epithelial to mesenchymal transition (EMT). This review summarizes the current knowledge on the phenomenon called “TGF-β1 paradox”, showing that better understanding of TGF-β1 functions can be a step towards development of new therapeutic approaches. According to current knowledge several drugs against TGF-β1 have been developed and are either in nonclinical or in early stages of clinical investigation.

scholarly journals The interplay of autophagy and epithelial-to-mesenchymal transition in cancer progression

2020 ◽  
Vol 7 (2) ◽  
pp. 8-19
Author(s):  
O. O. Ryabaya ◽  
A. A. Prokofieva
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Biological Processes ◽  
Antitumor Therapy ◽  
Mesenchymal Transition ◽  
New Strategy ◽  
Adverse Environmental Conditions ◽  
The One

Autophagy and epithelial-to-mesenchymal transition (EMT) are the main biological processes involved in tumor progression, and are closely linked. On the one hand, activation of autophagy provides energy and essential nutrients for EMT during the metastases spreading, which is required for tumor cells survival in adverse environmental conditions. On the other hand, autophagy, acting as a tumor suppressor, tends to inhibit metastasis by selectively suppressing the transcription factors of EMT in the early stages. Therefore, inhibition of EMT by inhibitors or inducers of autophagy may be a new strategy for antitumor therapy. Thus, the aim of this review is to highlight current knowledge about the crosstalk between autophagy and EMT processes in tumor progression and to summarize data supporting the necessity of parallel regulation of two processes through signaling pathways.

scholarly journals Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism

2020 ◽  
Vol 65 (4) ◽  
pp. R77-R90
Author(s):  
Frank A Simmen ◽  
Iad Alhallak ◽  
Rosalia C M Simmen
Keyword(s):  
Oxidative Stress ◽  
Malic Enzyme ◽  
Epithelial To Mesenchymal Transition ◽  
Cholesterol Biosynthesis ◽  
Intermediary Metabolism ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Transcriptional Target

Malic enzyme 1 (ME1) is a cytosolic protein that catalyzes the conversion of malate to pyruvate while concomitantly generating NADPH from NADP. Early studies identified ME1 as a mediator of intermediary metabolism primarily through its participatory roles in lipid and cholesterol biosynthesis. ME1 was one of the first identified insulin-regulated genes in liver and adipose and is a transcriptional target of thyroxine. Multiple studies have since documented that ME1 is pro-oncogenic in numerous epithelial cancers. In tumor cells, the reduction of ME1 gene expression or the inhibition of its activity resulted in decreases in proliferation, epithelial-to-mesenchymal transition and in vitro migration, and conversely, in promotion of oxidative stress, apoptosis and/or cellular senescence. Here, we integrate recent findings to highlight ME1’s role in oncogenesis, provide a rationale for its nexus with metabolic syndrome and diabetes, and raise the prospects of targeting the cytosolic NADPH network to improve therapeutic approaches against multiple cancers.

scholarly journals Tight junction proteins in gastrointestinal and liver disease

Gut ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 547-561 ◽  
Author(s):  
Mirjam B Zeisel ◽  
Punita Dhawan ◽  
Thomas F Baumert
Keyword(s):  
Liver Disease ◽  
Tight Junction ◽  
Functional Role ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Causative Role ◽  
Mesenchymal Transition ◽  
Disease Biology

Over the past two decades a growing body of evidence has demonstrated an important role of tight junction (TJ) proteins in the physiology and disease biology of GI and liver disease. On one side, TJ proteins exert their functional role as integral proteins of TJs in forming barriers in the gut and the liver. Furthermore, TJ proteins can also be expressed outside TJs where they play important functional roles in signalling, trafficking and regulation of gene expression. A hallmark of TJ proteins in disease biology is their functional role in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been established in the pathogenesis of colorectal cancer and gastric cancer. Among the best characterised roles of TJ proteins in liver disease biology is their function as cell entry receptors for HCV—one of the most common causes of hepatocellular carcinoma. At the same time TJ proteins are emerging as targets for novel therapeutic approaches for GI and liver disease. Here we review our current knowledge of the role of TJ proteins in the pathogenesis of GI and liver disease biology and discuss their potential as therapeutic targets.

scholarly journals Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1736
Author(s):  
Iuliu Sbiera ◽  
Stefan Kircher ◽  
Barbara Altieri ◽  
Martin Fassnacht ◽  
Matthias Kroiss ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Clinical Markers ◽  
Positive Role ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Epithelial Markers ◽  
Epithelial Cancers ◽  
Adrenocortical Adenomas ◽  
Slug Expression ◽  
The Impact

A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.

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