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Bioscience Reports Jan 2022Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of... (Review)
Review
Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors (TFs) including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT TFs and discussed their role in the process. We have also tried to focus on their mechanism of action, their interdependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type-dependent manner.
Topics: Animals; Antifibrotic Agents; Antineoplastic Agents; Embryonic Development; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Humans; Neoplasms; Phenotype; Signal Transduction; Transcription Factors; Wound Healing
PubMed: 34708244
DOI: 10.1042/BSR20211754 -
Cancer Treatment and Research... 2022Epithelial ovarian cancer is the second commonest cause of death amongst all gynaecological cancers. Treatment is challenging because almost 75% of cases are diagnosed... (Review)
Review
Epithelial ovarian cancer is the second commonest cause of death amongst all gynaecological cancers. Treatment is challenging because almost 75% of cases are diagnosed in advanced stages. Front line treatment with aggressive cytoreduction and adjuvant treatment decides the outcome. Despite the complete response to primary treatment majority will relapse with disease. Treatment options of recurrent disease depends on platinum free interval. Systemic therapy is the mainstay of treatment and secondary cytoreduction may be beneficial in selected patients Newer therapeutic agents are being added in the front line and recurrent setting to improve outcome.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Neoplasm Recurrence, Local; Cytoreduction Surgical Procedures
PubMed: 36127285
DOI: 10.1016/j.ctarc.2022.100629 -
Cell Research Feb 2009During development and in the context of different morphogenetic events, epithelial cells undergo a process called epithelial to mesenchymal transition or... (Review)
Review
During development and in the context of different morphogenetic events, epithelial cells undergo a process called epithelial to mesenchymal transition or transdifferentiation (EMT). In this process, the cells lose their epithelial characteristics, including their polarity and specialized cell-cell contacts, and acquire a migratory behavior, allowing them to move away from their epithelial cell community and to integrate into surrounding tissue, even at remote locations. EMT illustrates the differentiation plasticity during development and is complemented by another process, called mesenchymal to epithelial transition (MET). While being an integral process during development, EMT is also recapitulated under pathological conditions, prominently in fibrosis and in invasion and metastasis of carcinomas. Accordingly, EMT is considered as an important step in tumor progression. TGF-beta signaling has been shown to play an important role in EMT. In fact, adding TGF-beta to epithelial cells in culture is a convenient way to induce EMT in various epithelial cells. Although much less characterized, epithelial plasticity can also be regulated by TGF-beta-related bone morphogenetic proteins (BMPs), and BMPs have been shown to induce EMT or MET depending on the developmental context. In this review, we will discuss the induction of EMT in response to TGF-beta, and focus on the underlying signaling and transcription mechanisms.
Topics: Bone Morphogenetic Proteins; Cell Transdifferentiation; Epithelial Cells; Mesoderm; Signal Transduction; Smad Proteins; Transcription Factors; Transforming Growth Factor beta
PubMed: 19153598
DOI: 10.1038/cr.2009.5 -
American Journal of Respiratory Cell... Feb 2018The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the... (Review)
Review
The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.
Topics: Epithelial Cells; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Signal Transduction; Smoke; Smoking; Tight Junctions
PubMed: 28933915
DOI: 10.1165/rcmb.2017-0200TR -
Experimental & Molecular Medicine May 2017The intestine is a unique organ inhabited by a tremendous number of microorganisms. Intestinal epithelial cells greatly contribute to the maintenance of the symbiotic... (Review)
Review
The intestine is a unique organ inhabited by a tremendous number of microorganisms. Intestinal epithelial cells greatly contribute to the maintenance of the symbiotic relationship between gut microbiota and the host by constructing mucosal barriers, secreting various immunological mediators and delivering bacterial antigens. Mucosal barriers, including physical barriers and chemical barriers, spatially segregate gut microbiota and the host immune system to avoid unnecessary immune responses to gut microbes, leading to the intestinal inflammation. In addition, various immunological mediators, including cytokines and chemokines, secreted from intestinal epithelial cells stimulated by gut microbiota modulate host immune responses, maintaining a well-balanced relationship between gut microbes and the host immune system. Therefore, impairment of the innate immune functions of intestinal epithelial cells is associated with intestinal inflammation.
Topics: Animals; Bacteria; Bacterial Infections; Cytokines; Epithelial Cells; Gastrointestinal Microbiome; Homeostasis; Humans; Immunity, Innate; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice; Tight Junctions
PubMed: 28546564
DOI: 10.1038/emm.2017.20 -
Annals of Oncology : Official Journal... Oct 2013
Topics: Age Factors; Aging; Angiogenesis Inhibitors; Antineoplastic Agents; BRCA1 Protein; BRCA2 Protein; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Europe; Female; Follow-Up Studies; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Neovascularization, Pathologic; Ovarian Neoplasms; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 24078660
DOI: 10.1093/annonc/mdt333 -
Cell Reports Feb 2019Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the...
Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the apical enteroid surface is challenging because it is enclosed within the spheroid. We developed a technique to reverse enteroid polarity such that the apical surface everts to face the media. Apical-out enteroids maintain proper polarity and barrier function, differentiate into the major intestinal epithelial cell (IEC) types, and exhibit polarized absorption of nutrients. We used this model to study host-pathogen interactions and identified distinct polarity-specific patterns of infection by invasive enteropathogens. Salmonella enterica serovar Typhimurium targets IEC apical surfaces for invasion via cytoskeletal rearrangements, and Listeria monocytogenes, which binds to basolateral receptors, invade apical surfaces at sites of cell extrusion. Despite different modes of entry, both pathogens exit the epithelium within apically extruding enteroid cells. This model will enable further examination of IECs in health and disease.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Polarity; Epithelial Cells; Fatty Acids; Host-Pathogen Interactions; Humans; Intestinal Mucosa; Listeria monocytogenes; Models, Biological; Salmonella typhimurium; Spheroids, Cellular
PubMed: 30811997
DOI: 10.1016/j.celrep.2019.01.108 -
The International Journal of... 2022The movement of continuous sheets of epithelial cells occurs during embryonic development, tissue repair, and cancer. Common to cellular and molecular principles of...
The movement of continuous sheets of epithelial cells occurs during embryonic development, tissue repair, and cancer. Common to cellular and molecular principles of collective cell migration, invading cancers seem to reactivate embryonic pathways and patterns of cell movement. Epithelial cells possess the capability to become mesenchymal cells in a process called epithelial mesenchymal transition (EMT), which has been extensively studied and described. The aim of this article is to summarize the most recent literature data concerning less known epithelial-endothelial transition and endothelial-mesenchymal transition.
Topics: Cell Movement; Embryonic Development; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Humans; Neoplasms; Pregnancy
PubMed: 35238394
DOI: 10.1387/ijdb.210234dr -
Cells, Tissues, Organs 2022OVOL proteins (OVOL1 and OVOL2), vertebrate homologs of Drosophila OVO, are critical regulators of epithelial lineage determination and differentiation during embryonic... (Review)
Review
OVOL proteins (OVOL1 and OVOL2), vertebrate homologs of Drosophila OVO, are critical regulators of epithelial lineage determination and differentiation during embryonic development in tissues such as kidney, skin, mammary epithelia, and testis. OVOL can inhibit epithelial-mesenchymal transition and/or can promote mesenchymal-epithelial transition. Moreover, they can regulate the stemness of cancer cells, thus playing an important role during cancer cell metastasis. Due to their central role in differentiation and maintenance of epithelial lineage, OVOL overexpression has been shown to be capable of reprogramming fibroblasts to epithelial cells. Here, we review the roles of OVOL-mediated epithelial differentiation across multiple contexts, including embryonic development, cancer progression, and cellular reprogramming.
Topics: Cell Differentiation; DNA-Binding Proteins; Epithelial-Mesenchymal Transition; Female; Humans; Male; Neoplasms; Pregnancy; Skin; Transcription Factors
PubMed: 32932250
DOI: 10.1159/000511383