Special Issue "The Epithelial-to-Mesenchymal Transition (EMT) in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 May 2017)

Special Issue Editor

Guest Editor
Emeritus Prof. Dr. Joëlle Roche

Université de Poitiers, UMR-CNRS 7267, Laboratoire EBI, SEVE, F-86073 Poitiers, France
E-Mail
Interests: molecular biology of lung cancer; epigenetics (histone methyltransferase and HDAC inhibitors); epithelial-to-mesenchymal transition (EMT); guidance molecules (semaphorins and neuropilins)

Special Issue Information

Dear Colleagues,

The epithelial-to-mesenchymal transition (EMT) is a highly dynamic process with multiple transitional states, by which epithelial cells can convert into a mesenchymal phenotype. This process involves loss of cellular adhesion and cellular polarity, and an improvement in migratory and invasive properties. It occurs during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing. It is also involved in tumor progression with metastatic expansion, and plays a major role in resistance to cancer treatment. In cancers, EMT inducers are hypoxia, cytokines, and growth factors secreted by the tumor microenvironment, stroma crosstalk, metabolic changes, innate and adaptive immune responses, and treatment with antitumor drugs. Switch in gene expression from epithelial to mesenchymal phenotype is triggered by complex regulatory networks involving transcriptional control with SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47 among transcriptional factors, non-coding RNAs (miRNAs and long non-coding RNAs), chromatin remodeling and epigenetic modifications, alternative splicing, post-translational regulation, protein stability and subcellular localization. Reversion of EMT, the mesenchymal-to-epithelial transition (MET), affects circulating cancer cells when they reach a desirable metastatic niche to develop secondary tumors. More knowledge and control of EMT to MET is necessary and will be beneficial for patients for cancer treatment. This current Special Issue entitled “Epithelial to Mesenchymal Transition in Cancer” will address these questions.

Prof. Dr. Joëlle Roche
Guest Editor

Manuscript Submission Information

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Published Papers (16 papers)

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Editorial

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Open AccessEditorial The Epithelial-to-Mesenchymal Transition in Cancer
Received: 11 February 2018 / Revised: 13 February 2018 / Accepted: 13 February 2018 / Published: 16 February 2018
Cited by 5 | PDF Full-text (163 KB) | HTML Full-text | XML Full-text
Abstract
The epithelial-to-mesenchymal transition (EMT) occurs during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing.[...] Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)

Research

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Open AccessArticle Stem Cell-Like Properties of CK2β-down Regulated Mammary Cells
Received: 21 August 2017 / Revised: 21 August 2017 / Accepted: 28 August 2017 / Published: 31 August 2017
Cited by 2 | PDF Full-text (3632 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The ubiquitous protein kinase CK2 has been demonstrated to be overexpressed in a number of human tumours. This enzyme is composed of two catalytic α or α’ subunits and a dimer of β regulatory subunits whose expression levels are probably implicated in CK2 [...] Read more.
The ubiquitous protein kinase CK2 has been demonstrated to be overexpressed in a number of human tumours. This enzyme is composed of two catalytic α or α’ subunits and a dimer of β regulatory subunits whose expression levels are probably implicated in CK2 regulation. Several recent papers reported that unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition, a process involved in cancer invasion and metastasis. Herein, through transcriptomic and miRNA analysis together with comparison of cellular properties between wild type and CK2β-knock-down MCF10A cells, we show that down-regulation of CK2β subunit in mammary epithelial cells induces the acquisition of stem cell-like properties associated with perturbed polarity, CD44high/CD24low antigenic phenotype and the ability to grow under anchorage-independent conditions. These data demonstrate that a CK2β level establishes a critical cell fate threshold in the control of epithelial cell plasticity. Thus, this regulatory subunit functions as a nodal protein to maintain an epithelial phenotype and its depletion drives breast cell stemness. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Review

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Open AccessReview Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis
Cancers 2017, 9(12), 171; https://doi.org/10.3390/cancers9120171
Received: 9 November 2017 / Revised: 5 December 2017 / Accepted: 5 December 2017 / Published: 16 December 2017
Cited by 32 | PDF Full-text (638 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial to mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. [...] Read more.
Epithelial to mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. In this review, we discuss recent studies exploring novel regulation mechanisms of EMT in CRC, including the identification of new CRC EMT regulators. Upregulation of inducers can promote EMT, leading to increased invasiveness and metastasis in CRC. These inducers can downregulate E-cadherin and upregulate N-cadherin and vimentin (VIM) through modulating EMT-related signaling pathways, for instance WNT/β-catenin and TGF-β, and EMT transcription factors, such as zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. In addition, several microRNAs (miRNAs), including members of the miR-34 and miR-200 families, are found to target mRNAs of EMT-transcription factors, for example ZEB1, ZEB2, or SNAIL. Downregulation of these miRNAs is associated with distant metastasis and advanced stage tumors. Furthermore, the role of EMT in circulating tumor cells (CTCs) is also discussed. Mesenchymal markers on the surface of EMT CTCs were found to be associated with metastasis and could serve as potential biomarkers for metastasis. Altogether, these studies indicate that EMT is orchestrated by a complicated network, involving regulators of different signaling pathways. Further studies are required to understand the mechanisms underlying EMT in CRC. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessFeature PaperReview The Epithelial-to-Mesenchymal Transition in Breast Cancer: Focus on Basal-Like Carcinomas
Cancers 2017, 9(10), 134; https://doi.org/10.3390/cancers9100134
Received: 27 July 2017 / Revised: 13 September 2017 / Accepted: 28 September 2017 / Published: 30 September 2017
Cited by 13 | PDF Full-text (817 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer is a heterogeneous disease that is characterized by a high grade of cell plasticity arising from the contribution of a diverse range of factors. When combined, these factors allow a cancer cell to transition from an epithelial to a mesenchymal state [...] Read more.
Breast cancer is a heterogeneous disease that is characterized by a high grade of cell plasticity arising from the contribution of a diverse range of factors. When combined, these factors allow a cancer cell to transition from an epithelial to a mesenchymal state through a process of dedifferentiation that confers stem-like features, including chemoresistance, as well as the capacity to migrate and invade. Understanding the complex events that lead to the acquisition of a mesenchymal phenotype will therefore help to design new therapies against metastatic breast cancer. Here, we recapitulate the main endogenous molecular signals involved in this process, and their cross-talk with paracrine factors. These signals and cross-talk include the extracellular matrix; the secretome of cancer-associated fibroblasts, macrophages, cancer stem cells, and cancer cells; and exosomes with their cargo of miRNAs. Finally, we highlight some of the more promising therapeutic perspectives based on counteracting the epithelial-to-mesenchymal transition in breast cancer cells. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessFeature PaperReview The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis
Cancers 2017, 9(10), 131; https://doi.org/10.3390/cancers9100131
Received: 7 September 2017 / Revised: 22 September 2017 / Accepted: 25 September 2017 / Published: 27 September 2017
Cited by 3 | PDF Full-text (1141 KB) | HTML Full-text | XML Full-text
Abstract
Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays a key role in the regulation of the cell cycle. PLK1 is overexpressed in a variety of human tumors, and its expression level often correlates with increased cellular proliferation and poor prognosis in [...] Read more.
Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays a key role in the regulation of the cell cycle. PLK1 is overexpressed in a variety of human tumors, and its expression level often correlates with increased cellular proliferation and poor prognosis in cancer patients. It has been suggested that PLK1 controls cancer development through multiple mechanisms that include canonical regulation of mitosis and cytokinesis, modulation of DNA replication, and cell survival. However, emerging evidence suggests novel and previously unanticipated roles for PLK1 during tumor development. In this review, we will summarize the recent advancements in our understanding of the oncogenic functions of PLK1, with a focus on its role in epithelial-mesenchymal transition and tumor invasion. We will further discuss the therapeutic potential of these functions. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessFeature PaperReview EMT and Treatment Resistance in Pancreatic Cancer
Received: 27 July 2017 / Revised: 1 September 2017 / Accepted: 10 September 2017 / Published: 12 September 2017
Cited by 20 | PDF Full-text (672 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer (PC) is the third leading cause of adult cancer mortality in the United States. The poor prognosis for patients with PC is mainly due to its aggressive course, the limited efficacy of active systemic treatments, and a metastatic behavior, demonstrated throughout [...] Read more.
Pancreatic cancer (PC) is the third leading cause of adult cancer mortality in the United States. The poor prognosis for patients with PC is mainly due to its aggressive course, the limited efficacy of active systemic treatments, and a metastatic behavior, demonstrated throughout the evolution of the disease. On average, 80% of patients with PC are diagnosed with metastatic disease, and the half of those who undergo surgery and adjuvant therapy develop liver metastasis within two years. Metastatic dissemination is an early event in PC and is mainly attributed to an evolutionary biological process called epithelial-to-mesenchymal transition (EMT). This innate mechanism could have a dual role during embryonic growth and organ differentiation, and in cancer progression, cancer stem cell intravasation, and metastasis settlement. Many of the molecular pathways decisive in EMT progression have been already unraveled, but little is known about the causes behind the induction of this mechanism. EMT is one of the most distinctive and critical features of PC, occurring even in the very first stages of tumor development. This is known as pancreatic intraepithelial neoplasia (PanIN) and leads to early dissemination, drug resistance, and unfavorable prognosis and survival. The intention of this review is to shed new light on the critical role assumed by EMT during PC progression, with a particular focus on its role in PC resistance. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview The Role of Cancer-Derived Exosomes in Tumorigenicity & Epithelial-to-Mesenchymal Transition
Received: 31 May 2017 / Revised: 5 August 2017 / Accepted: 5 August 2017 / Published: 10 August 2017
Cited by 18 | PDF Full-text (1293 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes [...] Read more.
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30–100 nm membrane-bound vesicles that are formed and excreted by all cell types and released into the extracellular environment. Exosomal contents include DNA, mRNA, miRNA, as well as transmembrane- and membrane-bound proteins derived from their host cell contents. Exosomes are involved in intercellular signaling, both by membrane fusion to recipient cells with deposition of exosomal contents into the cytoplasm and by the binding of recipient cell membrane receptors. Recent work has implicated cancer-derived exosomes as an important mediator of intercellular signaling and EMT, with resultant transformation of cancer cells to a more aggressive phenotype, as well as the tropism of metastatic disease in specific cancer types with the establishment of the pre-metastatic niche. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer
Received: 9 June 2017 / Revised: 2 August 2017 / Accepted: 6 August 2017 / Published: 9 August 2017
Cited by 14 | PDF Full-text (2120 KB) | HTML Full-text | XML Full-text
Abstract
Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular [...] Read more.
Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypic plasticity, enabling mesenchymal-to-epithelial (MET) and epithelial-to-mesenchymal (EMT) transitions. In this review, we summarize current knowledge on EOC heterogeneity in an EMT context, outline major regulators of EMT in ovarian cancer, address controversies in EMT and EOC chemoresistance, and highlight computational modeling approaches toward understanding EMT/MET in EOC. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer
Received: 24 June 2017 / Revised: 17 July 2017 / Accepted: 26 July 2017 / Published: 3 August 2017
Cited by 20 | PDF Full-text (1256 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in [...] Read more.
Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription factors expression or microRNAs that occur in cancer promote EMT. Understanding the biology of EMT will help to define reversing process and treatment strategies. We will see that this complex mechanism is related to inflammation, cell mobility and stem cell features and that it is a dynamic process. The existence of intermediate phenotypes and tumour heterogeneity may be debated in the literature concerning EMT markers, EMT signatures and clinical consequences in NSCLC. However, given the role of EMT in metastasis and in drug resistance the development of EMT inhibitors is an interesting approach to counteract tumour progression and drug resistance. This review describes EMT involvement in cancer with an emphasis on NSCLC and microRNA regulation. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids
Received: 24 June 2017 / Revised: 20 July 2017 / Accepted: 26 July 2017 / Published: 29 July 2017
Cited by 10 | PDF Full-text (669 KB) | HTML Full-text | XML Full-text
Abstract
The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features [...] Read more.
The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-Yang) tool is integrated as a physiological strategy in embryonic development, as well as in the course of reparative or disease processes, prominently fibrosis, tumor invasion and metastasis. These mechanisms and their related signaling (e.g., TGF-β and BMPs) have been effectively studied in vitro by tissue-derived cell spheroids models. These three-dimensional (3D) cell culture systems, whose phenotype has been shown to be strongly dependent on TGF-β-regulated EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic in vivo micro-environment of tissue stem cell niches and their formation. These spheroids, therefore, nicely reproduce the finely regulated Ying-Yang equilibrium, which, together with other mechanisms, can be determinant in cell fate decisions in many pathophysiological scenarios, such as differentiation, fibrosis, regeneration, and oncogenesis. In this review, current progress in the knowledge of signaling pathways affecting EMT/MET and stemness regulation will be outlined by comparing data obtained from cellular spheroids systems, as ex vivo niches of stem cells derived from normal and tumoral tissues. The mechanistic correspondence in vivo and the possible pharmacological perspective will be also explored, focusing especially on the TGF-β-related networks, as well as others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its ability to convey multiple types of stimuli into relevant changes of the cell transcriptional program, can be regarded as a heterogeneous "stress-sensor" for EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a therapeutic target. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview Epithelial-to-Pericyte Transition in Cancer
Received: 3 May 2017 / Revised: 23 June 2017 / Accepted: 30 June 2017 / Published: 4 July 2017
Cited by 3 | PDF Full-text (5955 KB) | HTML Full-text | XML Full-text
Abstract
During epithelial-to-mesenchymal transition (EMT), cells lose epithelial characteristics and acquire mesenchymal properties. These two processes are genetically separable and governed by distinct transcriptional programs, rendering the EMT outputs highly heterogeneous. Our recent study shows that the mesenchymal products generated by EMT often express [...] Read more.
During epithelial-to-mesenchymal transition (EMT), cells lose epithelial characteristics and acquire mesenchymal properties. These two processes are genetically separable and governed by distinct transcriptional programs, rendering the EMT outputs highly heterogeneous. Our recent study shows that the mesenchymal products generated by EMT often express multiple pericyte markers, associate with and stabilize blood vessels to fuel tumor growth, thus phenotypically and functionally resembling pericytes. Therefore, some EMT events represent epithelial-to-pericyte transition (EPT). The serum response factor (SRF) plays key roles in both EMT and differentiation of pericytes, and may inherently confer the pericyte attributes on EMT cancer cells. By impacting their intratumoral location and cell surface receptor expression, EPT may enable cancer cells to receive and respond to angiocrine factors produced by the vascular niche, and develop therapy resistance. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview Epithelial-to-Mesenchymal Transition in the Pathogenesis and Therapy of Head and Neck Cancer
Received: 6 June 2017 / Revised: 27 June 2017 / Accepted: 30 June 2017 / Published: 3 July 2017
Cited by 7 | PDF Full-text (947 KB) | HTML Full-text | XML Full-text
Abstract
Head and neck cancer (HNC) is one of the most prevalent human malignancies worldwide, with a high morbidity and mortality. Implementation of interdisciplinary treatment modalities has improved the quality of life, but only minor changes in overall survival have been achieved over the [...] Read more.
Head and neck cancer (HNC) is one of the most prevalent human malignancies worldwide, with a high morbidity and mortality. Implementation of interdisciplinary treatment modalities has improved the quality of life, but only minor changes in overall survival have been achieved over the past decades. Main causes for treatment failure are an aggressive and invasive tumor growth in combination with a high degree of intrinsic or acquired treatment resistance. A subset of tumor cells gain these properties during malignant progression by reactivating a complex program of epithelia-to-mesenchymal transition (EMT), which is integral in embryonic development, wound healing, and stem cell behavior. EMT is mediated by a core set of key transcription factors, which are under the control of a large range of developmental signals and extracellular cues. Unraveling molecular principles that drive EMT provides new concepts to better understand tumor cell plasticity and response to established as well as new treatment modalities, and has the potential to identify new drug targets for a more effective, less toxic, and individualized therapy of HNC patients. Here, we review the most recent findings on the clinical relevance of a mesenchymal-like phenotype for HNC patients, including more rare cases of mucosal melanoma and adenoid cystic carcinoma. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression
Received: 22 May 2017 / Revised: 21 June 2017 / Accepted: 30 June 2017 / Published: 1 July 2017
Cited by 7 | PDF Full-text (1326 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial-mesenchymal transition (EMT) is a spatially- and temporally-regulated process involved in physiological and pathological transformations, such as embryonic development and tumor progression. While the role of TGF-β as an EMT-inducer has been extensively documented, the molecular mechanisms regulating this transition and their implications [...] Read more.
Epithelial-mesenchymal transition (EMT) is a spatially- and temporally-regulated process involved in physiological and pathological transformations, such as embryonic development and tumor progression. While the role of TGF-β as an EMT-inducer has been extensively documented, the molecular mechanisms regulating this transition and their implications in tumor metastasis are still subjects of intensive debates and investigations. TGF-β regulates EMT through both transcriptional and post-transcriptional mechanisms, and recent advances underline the critical roles of non-coding RNAs in these processes. Although microRNAs and lncRNAs have been clearly identified as effectors of TGF-β-mediated EMT, the contributions of other atypical non-coding RNA species, such as piRNAs, snRNAs, snoRNAs, circRNAs, and even housekeeping tRNAs, have only been suggested and remain largely elusive. This review discusses the current literature including the most recent reports emphasizing the regulatory functions of non-coding RNA in TGF-β-mediated EMT, provides original experimental evidence, and advocates in general for a broader approach in the quest of new regulatory RNAs. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessFeature PaperReview Epigenetic Regulation of the Epithelial to Mesenchymal Transition in Lung Cancer
Received: 29 May 2017 / Revised: 17 June 2017 / Accepted: 17 June 2017 / Published: 24 June 2017
Cited by 4 | PDF Full-text (981 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is the leading cause of cancer deaths worldwide. It is an aggressive and devastating cancer because of metastasis triggered by enhanced migration and invasion, and resistance to cytotoxic chemotherapy. The epithelial to mesenchymal transition (EMT) is a fundamental developmental process that [...] Read more.
Lung cancer is the leading cause of cancer deaths worldwide. It is an aggressive and devastating cancer because of metastasis triggered by enhanced migration and invasion, and resistance to cytotoxic chemotherapy. The epithelial to mesenchymal transition (EMT) is a fundamental developmental process that is reactivated in wound healing and a variety of diseases including cancer where it promotes migration/invasion and metastasis, resistance to treatment, and generation and maintenance of cancer stem cells. The induction of EMT is associated with reprogramming of the epigenome. This review focuses on major mechanisms of epigenetic regulation mainly in lung cancer with recent data on EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit ), the catalytic subunit of the PRC2 (Polycomb Group PcG), that behaves as an oncogene in lung cancer associated with gene repression, non-coding RNAs and the epitranscriptome. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Open AccessReview Phenotypic Plasticity and Cell Fate Decisions in Cancer: Insights from Dynamical Systems Theory
Received: 15 May 2017 / Revised: 13 June 2017 / Accepted: 13 June 2017 / Published: 22 June 2017
Cited by 11 | PDF Full-text (1714 KB) | HTML Full-text | XML Full-text
Abstract
Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype [...] Read more.
Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an “attractor” that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss the phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors”—hidden stable states of the underlying regulatory network that are not occupied by normal cells. Phenotypic transitions in cancer occur at varying levels depending on the context. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of therapy resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to therapies such as chemotherapy and androgen-deprivation therapy. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes “recanalization”, i.e., the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Other

Open AccessErratum Erratum: Roche, J. The Epithelial-to-Mesenchymal Transition in Cancer. Cancers, 2018, 10, 52
Received: 12 March 2018 / Revised: 12 March 2018 / Accepted: 13 March 2018 / Published: 19 March 2018
PDF Full-text (152 KB) | HTML Full-text | XML Full-text
Abstract
The author wishes to make the following correction to the paper[...] Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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