Author: Mohit Kumar Jolly Publisher: MDPI ISBN: 3039367242 Category : Medical Languages : en Pages : 512
Book Description
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: Mohit Kumar Jolly Publisher: ISBN: 9783039367252 Category : Languages : en Pages : 512
Book Description
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: Joëlle Roche Publisher: MDPI ISBN: 3038427934 Category : Science Languages : en Pages : 261
Book Description
This book is a printed edition of the Special Issue "The Epithelial-to-Mesenchymal Transition (EMT) in Cancer" that was published in Cancers
Author: Petranel Theresa Ferrao Publisher: Frontiers Media SA ISBN: 2889196623 Category : Cancer Languages : en Pages : 79
Book Description
The process of Epithelial-Mesenchymal-Transition (EMT) is known to result in a phenotype change in cells from a proliferative state to a more invasive state. EMT has been reported to drive the metastatic spread of various cancers and has also been associated with drug resistance to cytotoxics and targeted therapeutics. Recently phenotype switching akin to EMT has been reported in non-epithelial cancers such as metastatic melanoma. This process involves changes in EMT-Transcription Factors (EMT-TFs), suggesting that phenotype-switching may be common to several tumour types. It remains unclear as to whether the presence of both Epilthelial-like and Mesenchymal-like cells are a pre-requisite for phenotype switching within a tumour, how this heterogeneity is regulated, and if alteration of cell phenotype is sufficient to mediate migratory changes, or whether drivers of cell migration result in an associated phenotype switch in cancer cells. Similarly it has yet to be clarified if cells in an altered phenotype can be refractory to drug therapy or whether mediators of drug resistance induce a concurrent phenotypic change. Little is known today about the underlying genetic, epigenetic and transient changes that accompany this phenotypic switch and about the role for the tumor micro-environment in influencing it. Hence this is currently an area of speculation and keen interest in the Oncology field with wide-ranging translational implications. In this Frontiers Research Topic, we discuss our current understanding of these concepts in various cancer types including breast cancer, colorectal cancer and metastatic melanoma. This topic covers how these processes of cellular and phenotypic plasticity are regulated and how they relate to cancer initiation, progression, dormancy, metastases and response to cytotoxics or targeted therapies.
Author: David Cook Publisher: ISBN: Category : Languages : en Pages :
Book Description
Epithelial-mesenchymal plasticity (EMP) describes the interconversion of cells between epithelial and mesenchymal phenotypes. During the epithelial-mesenchymal transition (EMT), epithelial cells lose defining characteristics, such as stable cell-cell junctions, and gain the ability to migrate and invade through extracellular matrices. This plasticity contributes to tumour progression, promoting therapy resistance and immune cell evasion. Despite its importance, defining molecular features of this plasticity have largely remained elusive due to the limited scale of most studies. Here, I present my studies applying comparative single-cell genomics to map transcriptional changes associated with the EMT in diverse experimental conditions and EMP in tumours, I identify regulatory features associated with these dynamics, and explore opportunities to pharmacologically restrict them. This work provides critical steps towards building quantitative models of EMP, which will inform effective strategies to restrict these dynamics in cancer and improve patient prognosis.
Author: Marcus Andrew Ruscetti Publisher: ISBN: Category : Languages : en Pages : 286
Book Description
PTEN is one of the most commonly deleted tumor suppressor genes in human prostate cancer. Our group previously demonstrated that Pten deletion in the murine prostate epithelium recapitulates the disease progression seen in human prostate cancer, culminating in invasive adenocarcinoma. In addition to Pten loss endowing prostate cells with enhanced proliferative capacity, we found that Pten loss also led to the upregulation of inflammatory pathways, including Csf-1 and Il1b expression, within the prostate epithelium. These inflammatory cytokines recruit myeloid-derived suppressor cells (MDSCs) into the prostate, which subsequently promote an immune-suppressive tumor microenvironment and thereby facilitate tumor progression. Targeting immune-responsive pathways with the CSF-1R inhibitor GW2580 successfully inhibits MDSC infiltration and delays tumor progression. As Pten deletion alone does not produce distant macrometastasis, we surveyed additional pathways altered in human metastatic prostate cancer, and found that the RAS/MAPK pathway was significantly elevated in metastatic lesions. Indeed, when we combined Pten deletion with Kras activation in the prostate epithelium (Pb-Cre+/-;PtenL/L;KrasG12D/+) (CPK), we observed macrometastasis to the lungs and liver. Interestingly, within the prostate, we observed an epithelial-mesenchymal transition (EMT) phenotype, accompanied by significant upregulation of the EMT transcription factor Snail. Importantly, genetic deletion of Snail in CPK mice prevented distant macrometastasis, providing a mechanistic link between EMT and metastasis. To study the dynamic regulation of the EMT process, we crossed CPK mice with Vimentin-GFP reporter mice (CPKV), and were able to isolate populations of epithelial, EMT, and mesenchymal-like prostate tumor cells. We demonstrate that EMT and mesenchymal-like tumor cells have enhanced stem-like and tumor-initiating capacities and exhibit cellular plasticity in vivo. HMGA2, a chromatin remodeling protein, is significantly upregulated in EMT and mesenchymal-like tumor cells, as well as in human metastatic castration-resistant prostate cancer (mCRPC). Knockdown of Hmga2, or suppressing Hmga2 expression with the HDAC inhibitor LBH589, inhibits epithelial-mesenchymal plasticity and stemness activities in vitro and dramatically reduces prostate tumor burden and distant metastasis in vivo. Importantly, LBH589 in combination with castration significantly prolongs survival by targeting castration-resistant mesenchymal-like tumor cells and preventing mCRPC. LBH589 treatment in combination with androgen deprivation therapy may therefore be a promising treatment for patients with mCRPC.
Author: Roberto Piñeiro Publisher: Springer ISBN: 9783030358075 Category : Medical Languages : en Pages : 167
Book Description
This book is aimed to summarise the key aspects of the role of circulating tumour cells (CTCs) in breast cancer, with special attention to their contribution to tumour progression and establishment of metastatic disease. We aim to give a clear overview of the knowledge about CTCs, framed in the context of breast cancer, by analysing basic and clinical research carried out so far. In a broader sense, we will address what are the main clinical needs of this disease based on its molecular heterogeneity (subtypes) and lay out the knowledge and understanding that CTCs are giving about it and how they are contributing and can still improve the better monitoring and management of breast cancer patients. We will discuss the evidences of the use of CTCs as a tool to monitor cancer progression and therapy response, based on the prognostic and predictive value they have, as well as a tool to unravel mechanisms of resistance to therapy and to identify new biomarkers allowing to predict therapy success. Moreover, we will analyse the main aspects of ongoing clinical trials and how they can contribute to determine the clinical utility of CTCs as a breast cancer biomarker. We will also touch upon general knowledge or basic notions of the biology of the metastatic process in epithelial cancers, in order to understand the origin and biology of CTCs. In this sense, we will pay special attention to EMT (epithelial to mesenchymal transition), dormancy and minimal residual disease, three key aspects that determine the outcome of the disease. We will also cover general aspects on the isolation and characterization techniques applies to the study of CTCs, and also the possibilities that the study of CTCs, as a biomarker with biological function, is opening in terms of understanding the biology of metastatic cells and the identification of therapeutic targets based on the functional and molecular characterization of CTCs. Lastly, we will try to foresee the future of CTCs in terms of clinical application and implementation in the clinical routine.
Author: Sybille Mazurek Publisher: Springer ISBN: 3709118247 Category : Medical Languages : en Pages : 373
Book Description
The four sections of this book cover cell and molecular biology of tumor metabolism, metabolites, tumor microenvironment, diagnostics and epigenetics. Written by international experts, it provides a thorough insight into and understanding of tumor cell metabolism and its role in tumor biology. The book is intended for scientists in cancer cell and molecular biology, scientists in drug and diagnostic development, as well as for clinicians and oncologists.
Author: Mohit Kumar Jolly 
Author: Mohit Kumar Jolly
Author: Joëlle Roche
Author: Petranel Theresa Ferrao
Author: Satyendra Chandra Tripathi
Author: David Cook
Author: Marcus Andrew Ruscetti
Author: Roberto Piñeiro
Author: Sybille Mazurek
Author: Kyra Campbell