scholarly journals THE ROLE AND MECHANISMS OF EPITHELIAL-MESENCHYMAL TRANSITION IN THE PROGRESSION OF MELANOMA

2020 ◽  
Vol 19 (4) ◽  
pp. 8-17
Author(s):  
S. V. Chulkova ◽  
D. A. Ryabchikov ◽  
I. A. Dudina ◽  
I. V. Savchenko ◽  
A. V. Egorova ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Epithelial Mesenchymal Transition ◽  
Deep Understanding ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Modern Medicine ◽  
Mesenchymal Transition ◽  
Melanoma Progression ◽  
Leading Role ◽  
Developing Area

Despite the achievements of modern medicine in the diagnosis and treatment of oncological diseases, skin melanoma remains one of the leading causes of death worldwide: every third case of melanoma ends in death. As you know, one of the main causes of death is the high incidence of melanoma progression. It is important to note that the mechanisms of melanoma progression are diverse and the rapidly developing area of drug therapy for tumors requires a deep understanding of their characteristics. This is primarily due to the fact that these processes lead to the formation of special, minor tumor clones with stem properties. They are highly resistant to therapy. The latter is the mainobstacle to effective treatment of melanoma patients. The epithelial-mesenchymal transition (EMT) plays a leading role in the acquisition of metastatic potential by melanoma cells. An important distinguishing feature of EMT is a change in the level of expression of transmembrane glycoproteins involved in cell adhesion. With EMT, both a decrease in the level of E-cadherin and an increase in the expression of N-cadherin are observed. Such a switch in different classes of adhesion molecules leads to the fact that melanoma cells lose contact with neighboring keratinocytes and begin to interact with fibroblasts and endothelial cells. The key regulator in EMT induction in melanoma is the Notch1 signaling pathway, which accelerates N-cadherin expression when activated. In addition, EMT also regulates many other pathways – RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, the dysregulation of which is associated with the development of drug resistance in melanoma. The analysis was carried out in the article of modern literature data on the importance of EMT in carcinogenesis and prognosis of melanoma. The modern mechanisms of EMT, currently known prognostic factors, as well as potential therapeutic targets that affect EMT and, accordingly, inhibit the process of metastasis, are described in detail.

scholarly journals Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells

Oncotarget ◽  
2016 ◽  
Vol 7 (13) ◽  
pp. 15738-15746 ◽  
Author(s):  
Li Tang ◽  
Xue-Mei Yi ◽  
Jia Chen ◽  
Fu-Juan Chen ◽  
Wei Lou ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Epithelial Mesenchymal Transition ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Melanoma Progression

scholarly journals lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

2021 ◽  
Author(s):  
Weili Min ◽  
Liangzhang Sun ◽  
Burong Li ◽  
Xiao Gao ◽  
Shuqun Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Metastatic Potential ◽  
Caspase 8 ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Signaling Axis ◽  
Lung Adenocarcinoma Cells ◽  
Paclitaxel Liposome

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.

scholarly journals An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1060 ◽  
Author(s):  
Gastón Barbero ◽  
María Victoria Castro ◽  
María Belén Villanueva ◽  
María Josefina Quezada ◽  
Natalia Brenda Fernández ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Melanoma Cells ◽  
Dominant Negative ◽  
Migration And Invasion ◽  
Soluble Receptor ◽  
Mesenchymal Transition ◽  
Cytokines And Chemokines

Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-κB, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-κB subunit p65 as well as IKK phosphorylation and IκB degradation. By using cDNA overexpression, RNA interference, and dominant negative mutants we determined that ROR1, Dvl2, and Akt (from the Wnt5a pathway) and TRAF2 and RIP (from the NF-κB pathway) are required for the Wnt5a/NF-κB crosstalk. Wnt5a also induced p65 nuclear translocation and increased NF-κB activity as evidenced by reporter assays and a NF-κB-specific upregulation of RelB, Bcl-2, and Cyclin D1. Further, stimulation of melanoma cells with Wnt5a increased the secretion of cytokines and chemokines, including IL-6, IL-8, IL-11, and IL-6 soluble receptor, MCP-1, and TNF soluble receptor I. The inhibition of endogenous Wnt5a demonstrated that an autocrine Wnt5a loop is a major regulator of the NF-κB pathway in melanoma. Taken together, these results indicate that Wnt5a activates the NF-κB pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.

scholarly journals Functional Characterization of Cholinergic Receptors in Melanoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3141
Author(s):  
Anna Maria Lucianò ◽  
Ada Maria Tata
Keyword(s):  
Nervous System ◽  
Acetylcholine Receptors ◽  
Epithelial Mesenchymal Transition ◽  
Functional Characterization ◽  
Physiological Role ◽  
Melanoma Cells ◽  
Cholinergic Receptors ◽  
Mesenchymal Transition ◽  
Relevant Role

In the last two decades, the scientific community has come to terms with the importance of non-neural acetylcholine in light of its multiple biological and pathological functions within and outside the nervous system. Apart from its well-known physiological role both in the central and peripheral nervous systems, in the autonomic nervous system, and in the neuromuscular junction, the expression of the acetylcholine receptors has been detected in different peripheral organs. This evidence has contributed to highlight new roles for acetylcholine in various biological processes, (e.g., cell viability, proliferation, differentiation, migration, secretion). In addition, growing evidence in recent years has also demonstrated new roles for acetylcholine and its receptors in cancer, where they are involved in the modulation of cell proliferation, apoptosis, angiogenesis, and epithelial mesenchymal transition. In this review, we describe the functional characterization of acetylcholine receptors in different tumor types, placing attention on melanoma. The latest set of data accessible through literature, albeit limited, highlights how cholinergic receptors both of muscarinic and nicotinic type can play a relevant role in the migratory processes of melanoma cells, suggesting their possible involvement in invasion and metastasis.

scholarly journals The Cuban Propolis Component Nemorosone Inhibits Proliferation and Metastatic Properties of Human Colorectal Cancer Cells

2020 ◽  
Vol 21 (5) ◽  
pp. 1827 ◽  
Author(s):  
Yahima Frión-Herrera ◽  
Daniela Gabbia ◽  
Michela Scaffidi ◽  
Letizia Zagni ◽  
Osmany Cuesta-Rubio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Folk Remedies ◽  
Main Component

The majority of deaths related to colorectal cancer (CRC) are associated with the metastatic process. Alternative therapeutic strategies, such as traditional folk remedies, deserve attention for their potential ability to attenuate the invasiveness of CRC cells. The aim of this study is to investigate the biological activity of brown Cuban propolis (CP) and its main component nemorosone (NEM) and to describe the molecular mechanism(s) by which they inhibit proliferation and metastatic potential of 2 CRC cell lines, i.e., HT-29 and LoVo. Our results show that CP and NEM significantly decreased cell viability and inhibited clonogenic capacity of CRC cells in a dose and time-dependent manner, by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Furthermore, CP and NEM downregulated BCL2 gene expression and upregulated the expression of the proapoptotic genes TP53 and BAX, with a consequent activation of caspase 3/7. They also attenuated cell migration and invasion by inhibiting MMP9 activity, increasing E-cadherin and decreasing β-catenin and vimentin expression, proteins involved in the epithelial–mesenchymal transition (EMT). In conclusion NEM, besides displaying antiproliferative activity on CRC cells, is able to decrease their metastatic potential by modulating EMT-related molecules. These finding provide new insight about the mechanism(s) of the antitumoral properties of CP, due to NEM content.

scholarly journals TrkB-Induced Inhibition of R-SMAD/SMAD4 Activation is Essential for TGF-β-Mediated Tumor Suppressor Activity

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1048
Author(s):  
Min Soo Kim ◽  
Wook Jin
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathway ◽  
Tumor Suppression ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Suppressor Activity ◽  
Mesenchymal Transition ◽  
Stat3 Signaling Pathway ◽  
Tumor Suppressor Activity

TrkB-mediated activation of the IL6/JAK2/STAT3 signaling pathway is associated with the induction of the epithelial–mesenchymal transition (EMT) program and the acquisition of metastatic potential by tumors. Conversely, the transforming of growth factor-β (TGF-β) is implicated in tumor suppression through the canonical SMAD-dependent signaling pathway. Hence, TrkB could play a role in disrupting the potent TGF-β-mediated growth inhibition, a concept that has not been fully explored. Here, we identified TrkB to be a crucial regulator of the TGF-β signaling pathway as it inhibits the TGF-β-mediated tumor suppression and the activation of TrkB kinase. We further show that the interactions between TrkB and SMADs inhibit TGF-β-mediated R-SMAD/SMAD4 complex formation and suppress TGF-β-induced nuclear translocation and target gene expression. Additionally, the knockdown of TrkB restored the tumor inhibitory activity of TGF-β signaling. These observations suggest that interactions between TrkB and SMADs are critical for the inhibition of TGF-β tumor suppressor activity in cancer cells.

Extracellular vesicles: their role in cancer biology and epithelial–mesenchymal transition

2016 ◽  
Vol 474 (1) ◽  
pp. 21-45 ◽  
Author(s):  
Shashi K. Gopal ◽  
David W. Greening ◽  
Alin Rai ◽  
Maoshan Chen ◽  
Rong Xu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Cell Communication ◽  
Metastatic Potential ◽  
Messenger Rnas ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Cell–cell communication is critical across an assortment of physiological and pathological processes. Extracellular vesicles (EVs) represent an integral facet of intercellular communication largely through the transfer of functional cargo such as proteins, messenger RNAs (mRNAs), microRNA (miRNAs), DNAs and lipids. EVs, especially exosomes and shed microvesicles, represent an important delivery medium in the tumour micro-environment through the reciprocal dissemination of signals between cancer and resident stromal cells to facilitate tumorigenesis and metastasis. An important step of the metastatic cascade is the reprogramming of cancer cells from an epithelial to mesenchymal phenotype (epithelial–mesenchymal transition, EMT), which is associated with increased aggressiveness, invasiveness and metastatic potential. There is now increasing evidence demonstrating that EVs released by cells undergoing EMT are reprogrammed (protein and RNA content) during this process. This review summarises current knowledge of EV-mediated functional transfer of proteins and RNA species (mRNA, miRNA, long non-coding RNA) between cells in cancer biology and the EMT process. An in-depth understanding of EVs associated with EMT, with emphasis on molecular composition (proteins and RNA species), will provide fundamental insights into cancer biology.

scholarly journals Knockdown of 14-3-3γ Suppresses Epithelial–Mesenchymal Transition and Reduces Metastatic Potential of Human Non-small Cell Lung Cancer Cells

2018 ◽  
Vol 38 (6) ◽  
pp. 3507-3514 ◽  
Author(s):  
PRITSANA RAUNGRUT ◽  
ANUSARA WONGKOTSILA ◽  
NIDANUT CHAMPOOCHANA ◽  
KRIENGSAK LIRDPRAPAMONGKOL ◽  
JISNUSON SVASTI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition
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