scholarly journals Mechanisms of Disease: epithelial–mesenchymal transition—does cellular plasticity fuel neoplastic progression?

2008 ◽  
Vol 5 (5) ◽  
pp. 280-290 ◽  
Author(s):  
Eva A Turley ◽  
Mandana Veiseh ◽  
Derek C Radisky ◽  
Mina J Bissell
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Neoplastic Progression ◽  
Cellular Plasticity ◽  
Mesenchymal Transition

scholarly journals An Integrated View of Virus-Triggered Cellular Plasticity Using Boolean Networks

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2863
Author(s):  
Jenny Paola Alfaro-García ◽  
María Camila Granados-Alzate ◽  
Miguel Vicente-Manzanares ◽  
Juan Carlos Gallego-Gómez
Keyword(s):  
Cell Biology ◽  
Epithelial Mesenchymal Transition ◽  
Boolean Networks ◽  
Cellular Plasticity ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Logical Operators ◽  
Cell Tissue ◽  
Resource Exhaustion ◽  
Modeling Data

Virus-related mortality and morbidity are due to cell/tissue damage caused by replicative pressure and resource exhaustion, e.g., HBV or HIV; exaggerated immune responses, e.g., SARS-CoV-2; and cancer, e.g., EBV or HPV. In this context, oncogenic and other types of viruses drive genetic and epigenetic changes that expand the tumorigenic program, including modifications to the ability of cancer cells to migrate. The best-characterized group of changes is collectively known as the epithelial–mesenchymal transition, or EMT. This is a complex phenomenon classically described using biochemistry, cell biology and genetics. However, these methods require enormous, often slow, efforts to identify and validate novel therapeutic targets. Systems biology can complement and accelerate discoveries in this field. One example of such an approach is Boolean networks, which make complex biological problems tractable by modeling data (“nodes”) connected by logical operators. Here, we focus on virus-induced cellular plasticity and cell reprogramming in mammals, and how Boolean networks could provide novel insights into the ability of some viruses to trigger uncontrolled cell proliferation and EMT, two key hallmarks of cancer.

scholarly journals Functional balance between Tcf21–Slug defines cellular plasticity and migratory modalities in high grade serous ovarian cancer cell lines

2019 ◽  
Vol 41 (4) ◽  
pp. 515-526 ◽  
Author(s):  
Sagar S Varankar ◽  
Madhuri More ◽  
Ancy Abraham ◽  
Kshama Pansare ◽  
Brijesh Kumar ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Metastasis ◽  
Drug Exposure ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
High Grade ◽  
Cellular Plasticity ◽  
Ovarian Adenocarcinoma ◽  
Mesenchymal Transition

Abstract Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis that can be initiated by single cell epithelial to mesenchymal transition (EMT) or cooperative cell migration (CCM). Our study identifies novel regulatory cross-talks between Tcf21 and Slug in mediating phenotypic and migration plasticity in high-grade serous ovarian adenocarcinoma (HGSC). Differential expression and subcellular localization associate Tcf21, Slug with epithelial, mesenchymal phenotypes, respectively; however, gene manipulation approaches identify their association with additional intermediate phenotypic states, implying the existence of a multistep epithelial-mesenchymal transition program. Live imaging further associated distinct migratory modalities with the Tcf21/Slug status of cell systems and discerned proliferative/passive CCM, active CCM and EMT modes of migration. Tcf21–Slug balance identified across a phenotypic spectrum in HGSC cell lines, associated with microenvironment-induced transitions and the emergence of an epithelial phenotype following drug exposure. Phenotypic transitions and associated functionalities following drug exposure were affirmed to ensue from occupancy of Slug promoter E-box sequences by Tcf21. Our study effectively provides a framework for understanding the relevance of ovarian cancer plasticity as a function of two transcription factors.

Cellular Plasticity–Targeted Therapy in Head and Neck Cancers

2018 ◽  
Vol 97 (6) ◽  
pp. 654-664 ◽  
Author(s):  
W. Shang ◽  
Q. Zhang ◽  
Y. Huang ◽  
R. Shanti ◽  
F. Alawi ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Epigenetic Modification ◽  
High Rate ◽  
Treatment Modalities ◽  
Therapeutic Resistance ◽  
Cellular Plasticity ◽  
Mesenchymal Transition

Head and neck cancer is one of the most frequent human malignancies worldwide, with a high rate of recurrence and metastasis. Head and neck squamous cell carcinoma (HNSCC) is cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like properties, called cancer stem cells (CSCs). Epithelial-mesenchymal transition, gene mutation, and epigenetic modification are associated with the formation of cellular plasticity of tumor cells in HNSCC, contributing to the acquisition of invasive, recurrent, and metastatic properties and therapeutic resistance. Tumor microenvironment (TME) plays a supportive role in the initiation, progression, and metastasis of head and neck cancer. Stromal fibroblasts, vasculature, immune cells, cytokines, and hypoxia constitute the main components of TME in HNSCC, which contributes not only to the acquisition of CSC properties but also to the recurrence and therapeutic resistance of the malignancies. In this review, we discuss the potential mechanisms underlying the development of cellular plasticity, especially the emergence of CSCs, in HNSCC. We also highlight recent studies implicating the complex interplays among TME components, plastic CSCs, tumorigenesis, recurrence, and therapeutic resistance of HNSCC. Finally, we summarize the treatment modalities of HNSCC and reinforce the novel concept of therapeutic targeting CSCs in HNSCC.

scholarly journals Role of gp91phoxHomolog Nox1 in Induction of Premalignant Spindle Phenotypes of HPV 16 E6/E7—Immortalized Human Keratinocytes

2010 ◽  
Vol 10 ◽  
pp. 1435-1449 ◽  
Author(s):  
Walee Chamulitrat
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Cell Transformation ◽  
Human Keratinocytes ◽  
Human Colon ◽  
Neoplastic Progression ◽  
Mesenchymal Transition ◽  
Cytoskeleton Remodeling ◽  
Prostate Cancers ◽  
Nox Family

The NADPH oxidase (Nox) family of superoxide- and hydrogen peroxide—producing proteins has been recognized as important for signal transduction that regulates receptor-mediated functions, including cytoskeleton remodeling, cell proliferation, migration, differentiation, and cell death. Nox1 was the first of the Nox catalytic subunits to be cloned and shown to induce tumorigenic conversion of mouse fibroblasts. While Nox1 has been shown to be expressed in human colon and prostate cancers, however, limited studies have demonstrated the involvement of Nox1 in an early step of cell transformation. The aim of this review is to provide an overview on the role of Nox1 in cancer, as well as the contribution of our studies to demonstrate the involvement of Nox1 on neoplastic progression of human keratinocytes beyond the immortalization step. The generation of spindle phenotypes concomitant with anchorage-independent growth and invasiveness will be highlighted and discussed in relation to the possible role of Nox1 in epithelial-mesenchymal transition. Understanding these mechanisms may provide insight into Nox1 and redox signaling components as potential therapeutic targets to inhibit tumor progression.

scholarly journals Ki-67 promotes sequential stages of tumourigenesis by enabling cellular plasticity

2019 ◽  
Author(s):  
K. Mrouj ◽  
P. Singh ◽  
M. Sobecki ◽  
G. Dubra ◽  
E. Al Ghoul ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
Cellular Plasticity ◽  
Ki 67 ◽  
Mesenchymal Transition ◽  
Polycomb Repressive Complex 2 ◽  
Drug Classes

ABSTRACTRecent studies have shown that the cell proliferation antigen Ki-67 is not required for cell proliferation. Here, we demonstrate that Ki-67 enables implementation of transcriptional programmes conferring cellular plasticity, and is required for each step of tumour initiation, growth and metastasis. Ki-67 knockout causes global transcriptome remodelling, which, in mammary carcinoma cells, inhibits the epithelial-mesenchymal transition in a polycomb-repressive complex 2-dependent manner. This results in suppression of stem cell characteristics and sensitisation to various drug classes. Cancer cells lacking Ki-67 proliferate normally in vivo, but tumour growth is inhibited due to disrupted angiogenesis, and metastasis is abrogated. Finally, mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumourigenesis. Thus, Ki-67, which is expressed in all proliferating cancer cells, confers the plasticity required for different steps of carcinogenesis.

scholarly journals Rac1 Signaling: From Intestinal Homeostasis to Colorectal Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 665 ◽  
Author(s):  
Larissa Kotelevets ◽  
Eric Chastre
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Biological Significance ◽  
Small Gtpase ◽  
Colorectal Carcinogenesis ◽  
Fine Tuning ◽  
General Context ◽  
Neoplastic Progression ◽  
Intestinal Homeostasis ◽  
Mesenchymal Transition

The small GTPase Rac1 has been implicated in a variety of dynamic cell biological processes, including cell proliferation, cell survival, cell-cell contacts, epithelial mesenchymal transition (EMT), cell motility, and invasiveness. These processes are orchestrated through the fine tuning of Rac1 activity by upstream cell surface receptors and effectors that regulate the cycling Rac1-GDP (off state)/Rac1-GTP (on state), but also through the tuning of Rac1 accumulation, activity, and subcellular localization by post translational modifications or recruitment into molecular scaffolds. Another level of regulation involves Rac1 transcripts stability and splicing. Downstream, Rac1 initiates a series of signaling networks, including regulatory complex of actin cytoskeleton remodeling, activation of protein kinases (PAKs, MAPKs) and transcription factors (NFkB, Wnt/β-catenin/TCF, STAT3, Snail), production of reactive oxygen species (NADPH oxidase holoenzymes, mitochondrial ROS). Thus, this GTPase, its regulators, and effector systems might be involved at different steps of the neoplastic progression from dysplasia to the metastatic cascade. After briefly placing Rac1 and its effector systems in the more general context of intestinal homeostasis and in wound healing after intestinal injury, the present review mainly focuses on the several levels of Rac1 signaling pathway dysregulation in colorectal carcinogenesis, their biological significance, and their clinical impact.

scholarly journals Genetically Engineered Lung Cancer Cells for Analyzing Epithelial–Mesenchymal Transition

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1644
Author(s):  
Michał Kiełbus ◽  
Jakub Czapiński ◽  
Joanna Kałafut ◽  
Justyna Woś ◽  
Andrzej Stepulak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Epithelial Mesenchymal Transition ◽  
Genetically Engineered ◽  
Lung Cancer Cells ◽  
Gene Marker ◽  
Cellular Plasticity ◽  
Mesenchymal Transition

Cell plasticity, defined as the ability to undergo phenotypical transformation in a reversible manner, is a physiological process that also exerts important roles in disease progression. Two forms of cellular plasticity are epithelial–mesenchymal transition (EMT) and its inverse process, mesenchymal–epithelial transition (MET). These processes have been correlated to the poor outcome of different types of neoplasias as well as drug resistance development. Since EMT/MET are transitional processes, we generated and validated a reporter cell line. Specifically, a far-red fluorescent protein was knocked-in in-frame with the mesenchymal gene marker VIMENTIN (VIM) in H2170 lung cancer cells. The vimentin reporter cells (VRCs) are a reliable model for studying EMT and MET showing cellular plasticity upon a series of stimulations. These cells are a robust platform to dissect the molecular mechanisms of these processes, and for drug discovery in vitro and in vivo in the future.

Epithelial, mesenchymal and hybrid epithelial/mesenchymal phenotypes and their clinical relevance in cancer metastasis

2017 ◽  
Vol 19 ◽  
Author(s):  
Minal Garg
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Strong Association ◽  
Experimental Studies ◽  
Tumour Cells ◽  
Cellular Plasticity ◽  
Mesenchymal Transition ◽  
Tumour Initiation ◽  
Regulatory Functions

Cancer metastasis occurs through local invasion of circulating tumour cells (CTCs), intravasation, transportation to distant sites, and their extravasation followed by colonisation at secondary sites. Epithelial–mesenchymal transition (EMT) is a normal developmental phenomenon, but its aberrant activation confers tumour cells with enhanced cell motility, metastatic properties, resistant to therapies and cancer stem cell (CSC) phenotype in epithelium-derived carcinoma.Experimental studies from various research papers have been reviewed to determine the factors, which interlink cancer stemness and cellular plasticity with EMT. Although existence of CSCs has been linked with EMT, nevertheless, there are controversies with the involvement of type of tumour cells, including cells with E (epithelial) and M (mesenchymal) phenotype alone or hybrid E/M phenotype in different types of cancers. Studies on CTCs with hybrid E/M phenotypes during different stages of cancer metastasis reveal strong association with tumour -initiation potential, cellular plasticity and types of cancer cells. Cells with the hybrid E/M state are strictly controlled by phenotypic stability factors coupled to core EMT decision-making circuits, miR200/ZEB and miR-34/Snail.Understanding the regulatory functions of EMT program in cancer metastasis can help us to characterise the biomarkers of prognostic and therapeutic potential. These biomarkers when targeted may act as metastatic suppressors, inhibit cellular plasticity and stemness ability of tumour cells and can block metastatic growth.

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