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Author : Tao Sun
Publisher : Frontiers Media SA
ISBN 13 : 2832516343
Total Pages : 120 pages
Book Rating : 4.8/5 (325 download)
Download or read book Epithelial-Mesenchymal Transition (EMT) as a Therapeutic Target in Cancer written by Tao Sun and published by Frontiers Media SA. This book was released on 2023-03-03 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Joëlle Roche
Publisher : MDPI
ISBN 13 : 3038427934
Total Pages : 261 pages
Book Rating : 4.0/5 (384 download)
Download or read book The Epithelial-to-Mesenchymal Transition (EMT) in Cancer written by Joëlle Roche and published by MDPI. This book was released on 2018-04-09 with total page 261 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "The Epithelial-to-Mesenchymal Transition (EMT) in Cancer" that was published in Cancers
Author : Cecilia Battistelli
Publisher : Frontiers Media SA
ISBN 13 : 2889635023
Total Pages : 219 pages
Book Rating : 4.8/5 (896 download)
Download or read book Molecular Mechanisms and New Therapeutic Targets in Epithelial to Mesenchymal Transition (EMT) and Fibrosis written by Cecilia Battistelli and published by Frontiers Media SA. This book was released on 2020-02-10 with total page 219 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Cecilia Battistelli
Publisher : Frontiers Media SA
ISBN 13 : 2832502563
Total Pages : 169 pages
Book Rating : 4.8/5 (325 download)
Download or read book Molecular Mechanisms and New Therapeutic Targets in Epithelial to Mesenchymal Transition (EMT) and Fibrosis, Volume II written by Cecilia Battistelli and published by Frontiers Media SA. This book was released on 2022-10-17 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Mohit Kumar Jolly
Publisher : MDPI
ISBN 13 : 3039367242
Total Pages : 512 pages
Book Rating : 4.0/5 (393 download)
Download or read book Epithelial-Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Author : Mariano Bizzarri
Publisher : Springer Nature
ISBN 13 : 3030328570
Total Pages : 493 pages
Book Rating : 4.0/5 (33 download)
Download or read book Approaching Complex Diseases written by Mariano Bizzarri and published by Springer Nature. This book was released on 2020-04-17 with total page 493 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume – for pharmacologists, systems biologists, philosophers and historians of medicine – points to investigate new avenues in pharmacology research, by providing a full assessment of the premises underlying a radical shift in the pharmacology paradigm. The pharmaceutical industry is currently facing unparalleled challenges in developing innovative drugs. While drug-developing scientists in the 1990s mostly welcomed the transformation into a target-based approach, two decades of experience shows that this model is failing to boost both drug discovery and efficiency. Selected targets were often not druggable and with poor disease linkage, leading to either high toxicity or poor efficacy. Therefore, a profound rethinking of the current paradigm is needed. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggest that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development, efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets.
Author : Erik W. Thompson
Publisher :
ISBN 13 : 9783805596213
Total Pages : 0 pages
Book Rating : 4.5/5 (962 download)
Download or read book Epithelial-mesenchymal Transitions: New Advances in Development, Fibrosis and Cancer written by Erik W. Thompson and published by . This book was released on 2010-12-13 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This special issue represents a progression through signaling processes, development, fibrosis and cancer, illustrating common underlying mechanisms and highlighting the growing recognition of therapeutic possibilities. Novel molecular pathways are shown in the context of known regulators, and many articles offer specific insights into therapeutic targeting. Not surprisingly, several articles relate to the signaling pathways activated by the common anchor transforming growth factor (TGF)-beta in relation to epithelial-mesenchymal transition (EMT). A number of new mechanisms with therapeutic implications are described, specifically the interplay between the non-Smad PI3 kinase-Akt-mTOR axis and EMT-associated invasion in response to TGF-beta, the unexpected role of c-Abl in repressing TGF-beta1-induced EMT, the cooperativity between oncostatin M, hepatocyte growth factor and TGF-beta1 in lung carcinoma EMT, and the roles of dystroglycan and periostin in developmental EMT associated with gastrulation and palate fusion, respectively. Collectively, the issue presents the full spectrum of interest in EMT today.
Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (946 download)
Download or read book A Normal Epithelial-Mesenchymal Transition as a Model for Studying Metastatic Onset written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genes and signaling pathways implicated in EMT and the invasiveness of breast cancers include FGF, Notch and T-box and Ets family transcription factors. Studies were performed relating to each of these pathways and factors. One aim goal was to examine the relationship between Notch signaling and the Brachyury T-box transcription factor. Through cloning and characterization of this gene it was shown that Brachyury is not a target of Notch signaling and does not function in mesoderm formation, and therefore EMT. A second T-box family member implicated in breast cancer progression, Tbx2, was cloned and characterization initiated. A polyclonal antibody was generated and antisense oligonucleotides synthesized to assay Tbx2 function during EMT. Additionally, three other T box family members were cloned; homologues of Tbx4/5, Tbx6 and T-brain/Eomes. To look at direct effectors of EMT, a series of experiments looking at members of the Rho GTPase family were initiated. Homologues of Rho, Rac and cdc42 were cloned and dominant negative/constitutively active forms of these proteins generated. The goal of this research is to provide an in vivo insight into the mechanism whereby adhesions are assembled and disassembled during BMT and metastasis and thereby identify potential targets for therapeutics aimed at preventing the spread of breast cancers.
Author :
Publisher :
ISBN 13 :
Total Pages : 368 pages
Book Rating : 4.:/5 (899 download)
Download or read book The Role of the Epithelial-mesenchymal Transition in Aggressive Tumour Phenotypes written by and published by . This book was released on 2014 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: The epithelial-mesenchymal transition (EMT) is an evolutionarily conserved developmental process characterized by the loss of intercellular contacts, changes in cell polarity and increased migration and invasion. EMT has recently been shown to have a significant impact on chemotherapy response and metastatic progression in cancer cells. We hypothesized that because EMT contributes to aggressive cancer phenotypes, expression profiles of key EMT modulators could be profiled in ovarian and prostate tumours to distinguish aggressive from non-aggressive disease. Our results demonstrated that increased EMT gene expression was correlated with chemotherapy resistance in ovarian cancer, and with higher Gleason pattern in prostate cancer, confirming an association between EMT and increased risk for cancer progression. This underscores the potential for EMT gene signatures to be used as clinically relevant predictive and prognostic biomarkers. Functional studies using in vitro models of Cisplatin-resistant ovarian cancer and invasive prostate cancer demonstrated that inhibition of EMT signaling, both through the dysregulation of key transcription factors (SNAI1, SNAI2, ZEB1), and repressed expression of phenotypically important genes such as VIM, SPARC, CLTC and HIF1A resulted in loss of aggressive attributes in these cell lines. This included re-sensitization of our ovarian cancer cells to the effects of Cisplatin, while significantly reducing cell migration and invasion in our prostate cancer cells, both in 2- and 3-dimensional culture models. Furthermore, using our prostate cancer knockdown cell lines, we were able to assess gene expression changes in response to single gene repression. As a result, those genes that appear to have the highest degree of connectivity within the context of our EMT network were identified, thus contributing to the overall understanding of EMT regulation. Ultimately, we have been able to assess the role of the epithelial-mesenchymal transition in aggressive tumour behaviours, such as resistance to chemotherapy and progression towards metastatic events. The results of this work indicate that gene expression signatures associated with EMT may be useful as predictive and prognostic biomarkers in various cancer types. Furthermore, gene knockdown studies have provided insight into EMT signaling network regulation, as well as the functional contribution of a number of genes to alterations in migratory and invasive cancer cell programs.
Author : Janine Marie Buonato
Publisher :
ISBN 13 :
Total Pages : 256 pages
Book Rating : 4.:/5 (952 download)
Download or read book Cell Signaling Regulatory Mechanisms Controlling Epithelial-mesenchymal Transition in Carcinoma written by Janine Marie Buonato and published by . This book was released on 2015 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epithelial-mesenchymal transition (EMT) is a cellular program normally engaged during development and wound healing that is hijacked in many cancers to drive metastasis and resistance to therapy. The clinical implications of EMT in cancer progression have driven efforts to understand the cellular processes controlling EMT induction. Transforming growth factor-beta (TGF [beta]) and expression of related transcription factors potentiate EMT induction through complex and incompletely understood mechanisms. In this thesis, we investigated specific intracellular signaling pathways controlling maintenance of mesenchymal characteristics and EMT induction in response to growth factors in lung and pancreatic carcinoma cells. In lung carcinoma cells, extracellular signal-regulated kinase-1/2 (ERK1/2) pathway activation, which promotes cell survival and proliferation, was required for complete EMT induction. Furthermore, chronic ERK1/2 inhibition reversed baseline mesenchymal traits while simultaneously augmenting cellular sensitivity to a clinically approved small molecule EGFR inhibitor in cell lines with multiple clinically relevant modes of therapy resistance. In both lung and pancreatic carcinoma cell lines, TGF-mediated EMT was enhanced by co-treatment with epidermal growth factor (EGF), as had been noted in other contexts. We demonstrated that the ability of EGF to enhance TGF [beta]-mediated EMT depended on SH2 domain-containing phosphatase-2 (SHP2) activation through tyrosine phosphorylated adapter binding, which is required for complete ERK1/2 activation. Though SHP2 was not directly engaged and activated by TGF [beta], SHP2 was required for TGF [beta]-mediated effects. Incomplete or transient effects of ERK inhibition and SHP2 depletion motivated subsequent systematic evaluation of cell signaling processes engaged during EMT induction to identify other pathways that control mesenchymal dedifferentiation in pancreatic carcinoma cells. We thus developed a data-driven computational model to predict the relationships between multivariate signaling events and EMT-associated phenotypes in response to combinations of TGF [beta], EGF, and hepatocyte growth factor (HGF). Signaling intermediates that co-varied most with mesenchymal traits provided novel potential targets to inhibit EMT phenotype acquisition or restore epithelial traits in carcinoma. Together, this thesis enhanced mechanistic understanding of EMT regulation by SHP2, identified novel strategies to reverse EMT phenotypes in carcinoma cells, and generated a quantitative model to understand mesenchymal dedifferentiation, which can be leveraged in the future to improve clinical outcomes for cancer patients.
Author :
Publisher :
ISBN 13 : 9789175498096
Total Pages : 40 pages
Book Rating : 4.4/5 (98 download)
Download or read book Induction of Epithelial-mesenchymal Transition (EMT) in Women's Cancer written by and published by . This book was released on 2015 with total page 40 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Tao Sun
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (115 download)
Download or read book Epithelial-Mesenchymal Transition and Its Regulation in Tumor Metastasis written by Tao Sun and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Epithelial-mesenchymal transition (EMT) plays a key role in cancer metastasis. This process is a complex, multi-functional, and tightly regulated developmental program. EMT has been extensively investigated, but the molecular regulation of its signaling pathway is highly complex. In this study, the different elements of EMT cascades that could be targeted were determined. Difficulties in translating the preclinical findings in routine clinic were also distinguished. Future research will provide insights into the activation and regulation of various EMT programs in different tumor types and at distinct stages of tumor development. These results will likely facilitate the development of early detection strategies and improve the therapeutic targeting of malignant solid tumors.
Author : Johanne Hadsbjerg
Publisher :
ISBN 13 :
Total Pages : 84 pages
Book Rating : 4.:/5 (861 download)
Download or read book Epithelial-mesenchymal Transition in Cancer written by Johanne Hadsbjerg and published by . This book was released on 2012 with total page 84 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Andrew Thomas Chang
Publisher :
ISBN 13 : 9781267434708
Total Pages : 89 pages
Book Rating : 4.4/5 (347 download)
Download or read book Dissecting the Molecular Mechanism of Epithelial-to-mesenchymal Transition in Development and in Twist-driven Tumor Metastasis written by Andrew Thomas Chang and published by . This book was released on 2012 with total page 89 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epithelial-to-mesenchymal transition (EMT) is a highly conserved cellular process through which polarized and stationary epithelial cells become highly motile mesenchymal cells. EMT is an essential cellular process during embryogenesis, such as mesoderm induction, and more recently has been shown to be an important step in cancer metastasis. In both cases, epithelial cells must break away from neighboring cells and migrate to a distant location. Even though EMT has an important role in development and pathogenesis, the molecular machinery that drives EMT in mesoderm development and cancer metastasis is far from being fully understood. Therefore, for my dissertation, I sought to characterize the mechanism of EMT in both processes to gain a better understanding of cell migration and morphogenesis. Twist is a known inducer of EMT and tumor invasion and metastasis. To understand how Twist regulates target gene expression, we applied chromatin immuno-precipitation coupled with high-throughput sequencing to characterize its genome-wide DNA binding patterns. Using this approach, we found that through cooperative binding, Twist recognizes an evolutionarily conserved double E-box motif to regulate transcription of target genes. Furthermore, we show that the highly conserved WR domain of Twist mediates the high affinity cooperative binding of Twist to the double E-box motif. Functionally, the WR domain is essential for the ability of Twist to promote EMT. To characterize EMT in mammalian mesoderm formation, we utilized the in vitro embryoid body model system that forms all three germ layers during differentiation. After establishing the embryoid body system as an effective ex vivo model to study mesoderm formation, I first characterized the expression profile of known EMT-inducing transcription factors during mesoderm development. By knocking down individual genes using shRNA, I identified several EMT transcription factors to be essential for mesoderm formation and began to elucidate how a group of EMT-inducing transcription factors function together to orchestrate mesoderm formation. By studying the molecular mechanism of EMT in development and cancer metastasis, we have gained a better understanding of EMT as an essential cellular process and as a possible therapeutic target to inhibit cancer progression.
Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (946 download)
Download or read book A Normal Epithelial-Mesenchymal Transition as a Model for Metastatic Onset written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genes and signaling pathways implicated in EMT and the invasiveness of breast cancers include FGF, Notch and T-box and Ets family transcription factors. One goal of this research was to examine the relationship between Notch signaling and the Brachyury T-box transcription factor. Through cloning and characterization of this gene it was shown that Brachyury is not a target of Notch signaling and does not function in mesoderm formation, and therefore EMT. A second T-box family member implicated in breast cancer progression, Tbx2/3, was cloned and characterized. A polyclonal antibody was generated and functional assays performed to determine the role of Tbx2/3 during development and to link these observations to the tumorigenesis observed in breast cancer patients with amplifications of chromosome region 17q23 containing the Tbx2 locus. FGF signaling was also further examined during this funding period but the results of these studies were inconclusive. Functional characterization of Ets factors and subtractive screens aimed at identifying genes regulated by Ets and Tbx2/3 were initiated through a collaborative effort. This effort involves the generation of cDNA macroarrays to facilitate the easy identification and cloning of such genes after subtraction.
Author : Erik W. Thompson
Publisher : S. Karger AG (Switzerland)
ISBN 13 : 9783805582520
Total Pages : 0 pages
Book Rating : 4.5/5 (825 download)
Download or read book Advances in Epithelial-mesenchymal Transitions written by Erik W. Thompson and published by S. Karger AG (Switzerland). This book was released on 2007 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The concept of epithelial-mesenchymal transitions (EMT) has brought valuable insights to the study of complex processes involved in early embryo development, wound healing, carcinoma progression or kidney fibrosis. Major advances are reported in identifying new model systems, transcriptional regulators (including chromatin structure and microRNA), specific signaling pathways, and effector molecules. In this special issue, recent developments in the EMT field are reviewed, including the first localizations of Snail proteins in human cancers. Snail signaling and targets are carefully explored in several systems. Another emerging signaling pathway discussed involves TGF-beta. Several new concepts are consolidated including partial EMT, resulting in a metastable phenotype in cancer systems, and reversed EMT, described during bladder cancer progression as a mesenchymal-epithelial transition. Some of the papers focus on the first therapeutic approaches and different microarray analysis approaches specifically targeting the EMT process. Basic and clinical reseachers, clinicians as well as graduate and PhD students in the fields of cell and developmental biology, oncology and nephrology will appreciate this multidisciplinary and up-to-date overview of the EMT process.
Author : José I López
Publisher : Mdpi AG
ISBN 13 : 9783036520544
Total Pages : 292 pages
Book Rating : 4.5/5 (25 download)
Download or read book Cell Motility and Cancer written by José I López and published by Mdpi AG. This book was released on 2021-10-29 with total page 292 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Special Issue is conceived as a forum for basic, translational, and clinical research related to cell directional motility mechanisms and tumor cell migration. Under such a generic umbrella, basic researchers in biology, systems biology, and other quantitative sciences, as well as in physiology and pharmacology, will have the opportunity to join clinical specialties in medical oncology, biochemistry, immunology, and pathology. Such unique convergence of disciplines will enrich the panorama of a central characteristic of malignant tumors' cell motility.
