scholarly journals Cellular glycosylation senses metabolic changes and modulates cell plasticity during epithelial to mesenchymal transition

2017 ◽  
Vol 247 (3) ◽  
pp. 481-491 ◽  
Author(s):  
Patricia Carvalho-cruz ◽  
Frederico Alisson-Silva ◽  
Adriane R. Todeschini ◽  
Wagner B. Dias
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Metabolic Changes ◽  
Cell Plasticity ◽  
Mesenchymal Transition

scholarly journals OMRT-11. The effect of microenvironment on glioblastoma stem cells therapeutic resistance

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii9-ii9
Author(s):  
Tamara Lah Turnsek ◽  
Barbara Breznik ◽  
Bernarda Majc ◽  
Metka Novak ◽  
Andrej Porčnik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Combined Treatment ◽  
Cell Plasticity ◽  
Glioblastoma Stem Cells ◽  
Mesenchymal Transition ◽  
Non Invasive ◽  
Differential Gene

Abstract Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process in physiologic processes and invasion of various types of carcinoma and glioblastoma (GBM) cells. EMT is activated and regulated by specific endogenous triggers in complex network of intercellular interactions and signaling pathways. The hallmark of cancer-linked EMT are intermediate states that show notable cell plasticity, characteristic of cancer stem cells (CSCs), including glioblastoma stem cells – GSCs. GSCs resistance to irradiation (IR) and temozolomide (TMZ) chemotherapy is responsible for early relapses, even at distant brain sites. As GSCs are mostly homing to their “niches” as slowly-dividing GSC-subtype, mimicking a proneural-like non- invasive phenotype PN-genotype, we assume that this, by undergoing an EMT-like transition, GSCs are-reprogrammed to an invasive mesenchymal (MES) GBs/GSCs phenotype in a processes, called PMT (1). However, it is not known, if and by which environmental cues within the niche, this transition of GSCs is induced in vivo. In this work, we are presenting the transriptome data obtained when we exposed GSC spheroids to irradiation alone, TMZ alone and to the combined treatment in vitro and compared their differential genetic fingerprints related to EMT/PMT transition to the GSCs PMT transition, when embedded in their natural microenvironment in the GBM organoid model. The differential gene expression upon GSCs therapeutic perturbation (when alone and vs in the tumoroid microenvironment) will reveal the effects of the major candidate genes, associated with micronevironmendt stromal cells and matrix are contributing their observed EMT/PMT transition of GSCs in vivo. •1. Majc, B., Sever, T., Zarić, M, Breznik, B., Turk, B, Lah Turnšek, T. Epithelial- to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. DOI: 10.1016/j.bbamcr.2020.118782

scholarly journals Cancer Stem Cell Plasticity – A Deadly Deal

2019 ◽  
Author(s):  
P. T. Archana ◽  
Saxena Kritika ◽  
Reshma Murali ◽  
Mohit Kumar Jolly ◽  
Radhika Nair
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Resistance ◽  
Extensive Investigation ◽  
Epigenetic Factors ◽  
Therapeutic Approaches ◽  
Cell Plasticity ◽  
Mesenchymal Transition ◽  
Recent Developments ◽  
High Level

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

scholarly journals Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3093
Author(s):  
Andrea Rodríguez-Alonso ◽  
Alba Casas-Pais ◽  
Daniel Roca-Lema ◽  
Begoña Graña ◽  
Gabriela Romay ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Drug Targets ◽  
Epithelial To Mesenchymal Transition ◽  
Specific Binding ◽  
Ubiquitin Ligases ◽  
Small Subset ◽  
E3 Ubiquitin Ligases ◽  
Cell Plasticity ◽  
Mesenchymal Transition

The epithelial–mesenchymal plasticity (EMP) is a process by which epithelial cells acquire the ability to dynamically switch between epithelial and mesenchymal phenotypic cellular states. Epithelial cell plasticity in the context of an epithelial-to-mesenchymal transition (EMT) confers increased cell motility, invasiveness and the ability to disseminate to distant sites and form metastasis. The modulation of molecularly defined targets involved in this process has become an attractive therapeutic strategy against cancer. Protein degradation carried out by ubiquitination has gained attention as it can selectively degrade proteins of interest. In the ubiquitination reaction, the E3 ubiquitin-ligases are responsible for the specific binding of ubiquitin to a small subset of target proteins, and are considered promising anticancer drug targets. In this review, we summarize the role of the E3 ubiquitin-ligases that control targeted protein degradation in cancer-EMT, and we highlight the potential use of the E3 ubiquitin-ligases as drug targets for the development of small-molecule drugs against cancer.

scholarly journals Deregulation of Transcriptional Enhancers in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3532
Author(s):  
Fatemeh Mirzadeh Azad ◽  
Yaser Atlasi
Keyword(s):  
Epigenetic Regulation ◽  
Adult Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Plasticity ◽  
Tumour Heterogeneity ◽  
Mesenchymal Transition ◽  
Transcriptional Enhancers ◽  
Control Gene Expression ◽  
Epigenetic Modifiers ◽  
External Cues

Epigenetic regulations can shape a cell’s identity by reversible modifications of the chromatin that ultimately control gene expression in response to internal and external cues. In this review, we first discuss the concept of cell plasticity in cancer, a process that is directly controlled by epigenetic mechanisms, with a particular focus on transcriptional enhancers as the cornerstone of epigenetic regulation. In the second part, we discuss mechanisms of enhancer deregulation in adult stem cells and epithelial-to-mesenchymal transition (EMT), as two paradigms of cell plasticity that are dependent on epigenetic regulation and serve as major sources of tumour heterogeneity. Finally, we review how genetic variations at enhancers and their epigenetic modifiers contribute to tumourigenesis, and we highlight examples of cancer drugs that target epigenetic modifications at enhancers.

scholarly journals RNA-Binding Protein La Mediates TGFβ-Induced Epithelial to Mesenchymal Transition and Cancer Stem Cell Properties

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 343
Author(s):  
Tilman Heise ◽  
Gunhild Sommer
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Cancer Tissue ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Background: the aberrant overexpression of predominantly nuclear localizing RNA-binding protein (RBP) La contributes to proliferation, mobility, and chemoresistance of cancer cells and tumor growth in mice. Methods: studies included cancer tissue microarrays (TMAs) analyses, cancer tissue data mining, transforming growth factor β (TGFβ)-induced cancer cell plasticity studies, three dimensional sphere growth, epithelial to mesenchymal transition (EMT) assays, analysis of cancer stem cell (CSC) marker expression, and post-translational modification of cancer-associated La protein. Results: we demonstrated that significant overexpression of RBP La in lung and head and neck cancer tissue correlates with poor overall survival. Furthermore, small interfering RNA-mediated depletion of La reduced proliferation and migration of cancer cells, blocked TGFβ-induced EMT, and diminished both EMT and CSC marker expression. Rescue experiments with La wildtype but not RNA chaperone domain activity-defective La mutant increased the expression of those cancer progression markers, suggesting a critical role of La’s RNA chaperone activity in this process. La depletion in cancer cells also significantly decreased sphere growth in the presence of TGFβ. Interestingly, TGFβ treatment induced phosphorylation of La at threonine 389 (pLaT389) only in adherents but not in 3D growing cultures. Conclusion: our study suggests that the TGFβ/AKT/pLaT389 signaling pathway regulates cancer cell plasticity.

scholarly journals A gene regulatory network to control EMT programs in development and disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hassan Fazilaty ◽  
Luciano Rago ◽  
Khalil Kass Youssef ◽  
Oscar H. Ocaña ◽  
Francisco Garcia-Asencio ◽  
...  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Epithelial To Mesenchymal Transition ◽  
Good Prognosis ◽  
Vertebrate Development ◽  
Cell Plasticity ◽  
Mesenchymal Transition ◽  
Gene Regulatory

Abstract The Epithelial to Mesenchymal Transition (EMT) regulates cell plasticity during embryonic development and in disease. It is dynamically orchestrated by transcription factors (EMT-TFs), including Snail, Zeb, Twist and Prrx, all activated by TGF-β among other signals. Here we find that Snail1 and Prrx1, which respectively associate with gain or loss of stem-like properties and with bad or good prognosis in cancer patients, are expressed in complementary patterns during vertebrate development and in cancer. We show that this complementarity is established through a feedback loop in which Snail1 directly represses Prrx1, and Prrx1, through direct activation of the miR-15 family, attenuates the expression of Snail1. We also describe how this gene regulatory network can establish a hierarchical temporal expression of Snail1 and Prrx1 during EMT and validate its existence in vitro and in vivo, providing a mechanism to switch and select different EMT programs with important implications in development and disease.

scholarly journals The Regulatory Role of MicroRNAs in EMT and Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Apostolos Zaravinos
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Epithelial To Mesenchymal Transition ◽  
Control Cell ◽  
Cell Plasticity ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Cell Architecture ◽  
Recent Developments

The epithelial to mesenchymal transition (EMT) is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.

scholarly journals Epithelial cell plasticity drives endoderm formation during gastrulation

2021 ◽  
Author(s):  
Katharina Scheibner ◽  
Silvia Schirge ◽  
Ingo Burtscher ◽  
Maren Büttner ◽  
Michael Sterr ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Epithelial Cell ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Germ Layer ◽  
Cell Plasticity ◽  
Mesenchymal Transition

AbstractIt is generally accepted that epiblast cells ingress into the primitive streak by epithelial-to-mesenchymal transition (EMT) to give rise to the mesoderm; however, it is less clear how the endoderm acquires an epithelial fate. Here, we used embryonic stem cell and mouse embryo knock‐in reporter systems to combine time-resolved lineage labelling with high-resolution single-cell transcriptomics. This allowed us to resolve the morphogenetic programs that segregate the mesoderm from the endoderm germ layer. Strikingly, while the mesoderm is formed by classical EMT, the endoderm is formed independent of the key EMT transcription factor Snail1 by mechanisms of epithelial cell plasticity. Importantly, forkhead box transcription factor A2 (Foxa2) acts as an epithelial gatekeeper and EMT suppressor to shield the endoderm from undergoing a mesenchymal transition. Altogether, these results not only establish the morphogenetic details of germ layer formation, but also have broader implications for stem cell differentiation and cancer metastasis.

scholarly journals Research models and mesenchymal/epithelial plasticity of osteosarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaobin Yu ◽  
Jason T. Yustein ◽  
Jianming Xu
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Young Patients ◽  
Cell Plasticity ◽  
Human Patient ◽  
Mesenchymal Transition ◽  
Abnormal Growth ◽  
Epithelial Plasticity ◽  
Canine Models ◽  
Surviving Rate

AbstractMost osteosarcomas (OSs) develop from mesenchymal cells at the bone with abnormal growth in young patients. OS has an annual incidence of 3.4 per million people and a 60–70% 5-year surviving rate. About 20% of OS patients have metastasis at diagnosis, and only 27% of patients with metastatic OS survive longer than 5 years. Mutation of tumor suppressors RB1, TP53, REQL4 and INK4a and/or deregulation of PI3K/mTOR, TGFβ, RANKL/NF-κB and IGF pathways have been linked to OS development. However, the agents targeting these pathways have yielded disappointing clinical outcomes. Surgery and chemotherapy remain the main treatments of OS. Recurrent and metastatic OSs are commonly resistant to these therapies. Spontaneous canine models, carcinogen-induced rodent models, transgenic mouse models, human patient-derived xenograft models, and cell lines from animal and human OSs have been developed for studying the initiation, growth and progression of OS and testing candidate drugs of OS. The cell plasticity regulated by epithelial-to-mesenchymal transition transcription factors (EMT-TFs) such as TWIST1, SNAIL, SLUG, ZEB1 and ZEB2 plays an important role in maintenance of the mesenchymal status and promotion of cell invasion and metastasis of OS cells. Multiple microRNAs including miR-30/9/23b/29c/194/200, proteins including SYT-SSX1/2 fusion proteins and OVOL2, and other factors that inhibit AMF/PGI and LRP5 can suppress either the expression or activity of EMT-TFs to increase epithelial features and inhibit OS metastasis. Further understanding of the molecular mechanisms that regulate OS cell plasticity should provide potential targets and therapeutic strategies for improving OS treatment.

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