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 Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4985
Author(s):  
Saima Usman ◽  
Naushin H. Waseem ◽  
Thuan Khanh Ngoc Nguyen ◽  
Sahar Mohsin ◽  
Ahmad Jamal ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cells ◽  
Type I ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Type Iii ◽  
Tumour Spread ◽  
Molecular Events

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.

scholarly journals Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

2019 ◽  
Vol 8 (4) ◽  
pp. 439 ◽  
Author(s):  
Hsiao-Chen Chiu ◽  
Chia-Jung Li ◽  
Giou-Teng Yiang ◽  
Andy Tsai ◽  
Meng-Yu Wu
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Cell Biology ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Cell Metabolism ◽  
Basic Research ◽  
Genetic Mutation ◽  
Molecular Regulation ◽  
Mesenchymal Transition

Endometrial carcinogenesis is involved in several signaling pathways and it comprises multiple steps. The four major signaling pathways—PI3K/AKT, Ras/Raf/MEK/ERK, WNT/β-catenin, and vascular endothelial growth factor (VEGF)—are involved in tumor cell metabolism, growth, proliferation, survival, and angiogenesis. The genetic mutation and germline mitochondrial DNA mutations also impair cell proliferation, anti-apoptosis signaling, and epithelial–mesenchymal transition by several transcription factors, leading to endometrial carcinogenesis and distant metastasis. The PI3K/AKT pathway activates the ransforming growth factor beta (TGF-β)-mediated endothelial-to-mesenchymal transition (EMT) and it interacts with downstream signals to upregulate EMT-associated factors. Estrogen and progesterone signaling in EMT also play key roles in the prognosis of endometrial carcinogenesis. In this review article, we summarize the current clinical and basic research efforts regarding the detailed molecular regulation in endometrial carcinogenesis, especially in EMT, to provide novel targets for further anti-carcinogenesis treatment.

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.

scholarly journals Modelling Biological Systems: A New Algorithm for the Inference of Boolean Networks

Mathematics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 373
Author(s):  
Mario Rubio-Chavarría ◽  
Cristina Santamaría ◽  
Belén García-Mora ◽  
Gregorio Rubio
Keyword(s):  
Traffic Management ◽  
Epithelial Mesenchymal Transition ◽  
Directed Graphs ◽  
Biological Systems ◽  
Computational Cost ◽  
Computation Time ◽  
Boolean Networks ◽  
Model Systems ◽  
Lac Operon ◽  
Mesenchymal Transition

Biological systems are commonly constituted by a high number of interacting agents. This great dimensionality hinders biological modelling due to the high computational cost. Therefore, new modelling methods are needed to reduce computation time while preserving the properties of the depicted systems. At this point, Boolean Networks have been revealed as a modelling tool with high expressiveness and reduced computing times. The aim of this work has been to introduce an automatic and coherent procedure to model systems through Boolean Networks. A synergy that harnesses the strengths of both approaches is obtained by combining an existing approach to managing information from biological pathways with the so-called Nested Canalising Boolean Functions (NCBF). In order to show the power of the developed method, two examples of an application with systems studied in the bibliography are provided: The epithelial-mesenchymal transition and the lac operon. Due to the fact that this method relies on directed graphs as a primary representation of the systems, its applications exceed life sciences into areas such as traffic management or machine learning, in which these graphs are the main expression of the systems handled.

scholarly journals MiR-937-3p promotes metastasis and angiogenesis and is activated by MYC in lung adenocarcinoma

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Zijian Ma ◽  
Ganyi Chen ◽  
Yiqian Chen ◽  
Zizhang Guo ◽  
Hao Chai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Biological Marker ◽  
Luciferase Reporter ◽  
Invasion And Metastasis ◽  
Luciferase Reporter Gene ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Abstract Background Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) accounts for more than half of all NSCLC cases in most countries. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear. Methods miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell migration, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tube formation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vivo experiments were performed on male NOD/SCID nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA. Result In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3′-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region. Conclusions Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, thereby promoting the progress of LUAD. We speculate that miR-937-3p can be used as a therapeutic target and potential biomarker for LUAD.

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 MiR-937-3p Promotes Metastasis and Angiogenesis and is Activated by MYC in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Zijian Ma ◽  
Ganyi Chen ◽  
Yiqian Chen ◽  
Zizhang Guo ◽  
Hao Chai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Biological Marker ◽  
Luciferase Reporter ◽  
Invasion And Metastasis ◽  
Luciferase Reporter Gene ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Abstract Background: Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) is the majority of NSCLC. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear.Methods: miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tubeformation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vitro experiments were performed on male BALB/c nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA.Result: In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3'-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region.Conclusion: Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, which is a therapeutic target and potential biomarker for LUAD.

scholarly journals The epithelial–mesenchymal transition: new insights in signaling, development, and disease

2006 ◽  
Vol 172 (7) ◽  
pp. 973-981 ◽  
Author(s):  
Jonathan M. Lee ◽  
Shoukat Dedhar ◽  
Raghu Kalluri ◽  
Erik W. Thompson
Keyword(s):  
Cell Biology ◽  
Epithelial Mesenchymal Transition ◽  
International Association ◽  
Mesenchymal Cell ◽  
Potential Contribution ◽  
Mesenchymal Transition ◽  
Scientific Debate ◽  
Pathway Activation ◽  
High Level

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a defining structural feature of organ development. Current interest in this process, which is described as an epithelial–mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1–3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the first being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal–epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, fibrosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and fibrosis, as well as the identification of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996–6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991–5995).

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