scholarly journals The Notch Pathway in Breast Cancer Progression

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Emmanuel N. Kontomanolis ◽  
Sofia Kalagasidou ◽  
Stamatia Pouliliou ◽  
Xanthoula Anthoulaki ◽  
Nikolaos Georgiou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Breast Cancer Progression ◽  
Notch Receptors ◽  
The Impact

Objective. Notch signaling pathway is a vital parameter of the mammalian vascular system. In this review, the authors summarize the current knowledge about the impact of the Notch signaling pathway in breast cancer progression and the therapeutic role of Notch’s inhibition.Methods. The available literature in MEDLINE, PubMed, and Scopus, regarding the role of the Notch pathway in breast cancer progression was searched for related articles from about 1973 to 2017 including terms such as “Notch,” “Breast Cancer,” and “Angiogenesis.”Results. Notch signaling controls the differentiation of breast epithelial cells during normal development. Studies confirm that the Notch pathway has a major participation in breast cancer progression through overexpression and/or abnormal genetic type expression of the notch receptors and ligands that determine angiogenesis. The cross-talk of Notch and estrogens, the effect of Notch in breast cancer stem cells formation, and the dependable Notch overexpression during breast tumorigenesis have been studied enough and undoubtedly linked to breast cancer development. The already applied therapeutic inhibition of Notch for breast cancer can drastically change the course of the disease.Conclusion. Current data prove that Notch pathway has a major participation and multiple roles during breast tumor progression. Inhibition of Notch receptors and ligands provides innovative therapeutic results and could become the therapy of choice in the next few years, even though further research is needed to reach safe conclusions.

scholarly journals Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
M. V. Giuli ◽  
E. Giuliani ◽  
I. Screpanti ◽  
D. Bellavia ◽  
S. Checquolo
Keyword(s):  
Breast Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Notch Receptors ◽  
Cancer Subtype

Triple-negative breast cancer (TNBC) is a subgroup of 15%-20% of diagnosed breast cancer patients. It is generally considered to be the most difficult breast cancer subtype to deal with, due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), which usually direct targeted therapies. In this scenario, the current treatments of TNBC-affected patients rely on tumor excision and conventional chemotherapy. As a result, the prognosis is overall poor. Thus, the identification and characterization of targets for novel therapies are urgently required. The Notch signaling pathway has emerged to act in the pathogenesis and tumor progression of TNBCs. Firstly, Notch receptors are associated with the regulation of tumor-initiating cells (TICs) behavior, as well as with the aetiology of TNBCs. Secondly, there is a strong evidence that Notch pathway is a relevant player in mammary cancer stem cells maintenance and expansion. Finally, Notch receptors expression and activation strongly correlate with the aggressive clinicopathological and biological phenotypes of breast cancer (e.g., invasiveness and chemoresistance), which are relevant characteristics of TNBC subtype. The purpose of this up-to-date review is to provide a detailed overview of the specific role of all four Notch receptors (Notch1, Notch2, Notch3, and Notch4) in TNBCs, thus identifying the Notch signaling pathway deregulation/activation as a pathognomonic feature of this breast cancer subtype. Furthermore, this review will also discuss recent information associated with different therapeutic options related to the four Notch receptors, which may be useful to evaluate prognostic or predictive indicators as well as to develop new therapies aimed at improving the clinical outcome of TNBC patients.

Association between Notch signaling pathway and cancer

2013 ◽  
Vol 19 (4) ◽  
pp. 427-437
Author(s):  
Nadežda Lachej ◽  
Janina Didžiapetrienė ◽  
Birutė Kazbarienė ◽  
Daiva Kanopienė ◽  
Violeta Jonušienė
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Treatment Method ◽  
Notch Signaling Pathway ◽  
Published Data ◽  
Undifferentiated Cells ◽  
Oncologic Diseases ◽  
Worse Prognosis

Background. The components of the Notch signaling pathway are important in maintaining the balance involved in cell proliferation, apoptosis and differentiation. Therefore, dysfunction of the Notch prevents differentiation, ultimately guiding undifferentiated cells toward malignant transformation. The aim of this article is to present recently published data concerning the role of the Notch signaling pathway components in development and prognosis of oncologic diseases, in occurrence of resistance to cytostatic agents and importance in creating of new cancer treatment approaches. Materials and methods. The Pubmed was the main source of looking for information for this article. Results. Recent investigations show that disorders of the Notch signaling pathway are associated with development of some human haematological and solid cancers. In different tissues and organs this active pathway can act as a tumor suppressor or an oncogene. Accordingly, the increased or decreased expression of its components is defined. Most of published data show that the increased expression of Notch pathway components correlates with a worse prognosis of cancer and a shorter survival. Recently, the Notch pathway has been reported to be involved in drug resistance. The modulation of the Notch signaling pathway could be helpful in treatment of some tumors with abnormal activity of this pathway’s components. Therefore changes in the expression of Notch components could become important predictive factors, helpful in selecting the proper treatment method. Conclusions. The results of recent studies are very important, since the detecting of the prognostic and predictive value of components of the Notch signaling pathway can allow creating new and improving already known methods of cancer diagnostic and treatment.

scholarly journals THE ROLE OF MRNA LEVEL OF THE NOTCH SIGNALING PATHWAY GENES IN INDUCED RAT LIVER FIBROGENESIS

2021 ◽  
Vol 20 (2) ◽  
pp. 25-37
Author(s):  
A.T. Shchastniy ◽  
◽  
E.I. Lebedeva ◽  
A.S. Babenka ◽  
◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Rat Liver ◽  
Mrna Level ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mrna Levels ◽  
Starting Point ◽  
Liver Fibrogenesis

Objectives. To study the role of mRNA level of the Notch signaling pathway genes in induced rat liver fibrogenesis. Material and methods. Fibrosis followed by the transition to liver cirrhosis in rats of Wistar line was induced with thioacetamide at a dose of 200 mg/kg of animal body weight twice a week for 17 weeks. The rats were randomized into 9 groups of 12 animals each. The mRNA level of the Notch signaling pathway genes was assessed by real-time PCR. The notch1, notch2, yap1 and hes1 genes were used as molecular targets. Microscopic analysis of histological preparations was performed using the OLYMPUS BX51 microscope. The degree of fibrosis was assessed according to the scale of Ishak K.G. Results. The study of the classical transcription factor of the Notch signaling pathway, hes1, revealed its very low and stable activity in all studied samples. The analysis of relative dynamics of the mRNA level of the notch1, notch2, and yap1 genes made it possible to determine marked changes in their levels at the point of transition from the normal state of liver tissues to the development of fibrosis. Conclusions. Within the framework of this study, the hes1 gene is not a target of the Notch pathway and can be used as a reference gene. The noted decrease in the mRNA level of the yap1 gene, probably, inhibits the compensatory-restorative processes in the liver, activates the stellate cells, and promotes the transformation of fibrosis into cirrhosis. In addition, it has been found that the revealed fluctuations in the mRNA levels of the notch1 and yap1 genes in relation to the starting point (there are no changes in the liver tissue) quite accurately describe the period of the onset of the transition of advanced fibrosis to cirrhosis. In this regard, they can be considered as potential markers of the transition of fibrosis to cirrhosis.

scholarly journals Linc00514 promotes breast cancer metastasis and M2 polarization of tumor-associated macrophages via Jagged1-mediated notch signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Sifeng Tao ◽  
Qiang Chen ◽  
Chen Lin ◽  
Haiying Dong
Keyword(s):  
Breast Cancer ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Notch Signaling Pathway ◽  
M2 Macrophage ◽  
M2 Polarization

Abstract Background Tumor-associated macrophages (TAMs) and tumor cells are important components of the tumor microenvironment. M2 polarization of TAMs, which is a major actor in breast cancer malignancy and metastasis, can be induced by breast cancer cells. However, the potential mechanisms of the interaction between breast cancer cells and TAMs remain unclear. Methods The candidate breast cancer-associated long non-coding RNAs (lncRNAs) were analyzed using the GEO database. Functional assays, including MTT assay, Transwell assay, and EdU labeling detection, were performed to investigate the oncogenic role of linc00514 in breast cancer progression. The co-culture and ELISA assays were used to assess the role of linc00514 in macrophage recruitment and M2 polarization. RNA immunoprecipitation, RNA pull-down, and luciferase reporter assays were applied to determine the mechanism of linc00514 in breast cancer metastasis. Mouse xenograft models, mouse pulmonary metastatic models, and mouse primary tumor models were used to assess the role of linc00514 in M2 macrophage polarization and breast cancer tumorigenicity. Results Linc00514 was highly expressed in clinical breast cancer tissues and breast cancer cell lines. Overexpression of linc00514 promoted the proliferation and invasion of breast cancer cells and increased xenograft tumor volumes and pulmonary metastatic nodules. Overexpression of linc00514 also increased the percentage of macrophages expressing M2 markers CD206 and CD163. Mechanistically, linc00514 promoted Jagged1 expression in a transcriptional manner by increasing the phosphorylation of a transcription factor STAT3. Subsequently, Jagged1-mediated Notch signaling pathway promoted IL-4 and IL-6 secretions in breast cancer cells and ultimately inducing M2 polarization of macrophages. Conclusion Linc00514 plays an important role in regulating breast cancer tumorigenicity and M2 macrophage polarization via Jagged1-mediated Notch signaling pathway.

scholarly journals Post-Developmental Roles of Notch Signaling in the Nervous System

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 985
Author(s):  
Jose L. Salazar ◽  
Sheng-An Yang ◽  
Shinya Yamamoto
Keyword(s):  
Nervous System ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Fruit Fly ◽  
Notch Signaling Pathway ◽  
Nervous System Development ◽  
Model Organisms ◽  
Cellular Models

Since its discovery in Drosophila, the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core Notch signaling components were initially identified through their dramatic ‘neurogenic’ phenotype of developing fruit fly embryos. Components of the Notch signaling pathway continue to be expressed in mature neurons and glia cells, which is suggestive of a role in the post-developmental nervous system. The Notch pathway has been, so far, implicated in learning and memory, social behavior, addiction, and other complex behaviors using genetic model organisms including Drosophila and mice. Additionally, Notch signaling has been shown to play a modulatory role in several neurodegenerative disease model animals and in mediating neural toxicity of several environmental factors. In this paper, we summarize the knowledge pertaining to the post-developmental roles of Notch signaling in the nervous system with a focus on discoveries made using the fruit fly as a model system as well as relevant studies in C elegans, mouse, rat, and cellular models. Since components of this pathway have been implicated in the pathogenesis of numerous psychiatric and neurodegenerative disorders in human, understanding the role of Notch signaling in the mature brain using model organisms will likely provide novel insights into the mechanisms underlying these diseases.

scholarly journals Cis-activation in the Notch signaling pathway

2018 ◽  
Author(s):  
Nagarajan Nandagopal ◽  
Leah A. Santat ◽  
Michael B. Elowitz
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Single Cells ◽  
Notch Pathway ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Activation Process ◽  
Notch Receptors ◽  
Ligand Expression ◽  
Multiple Ligand

AbstractThe Notch signaling pathway consists of transmembrane ligands and receptors that can interact both within the same cell (cis) and across cell boundaries (trans). Previous work has shown that cis-interactions act to inhibit productive signaling. Here, by analyzing Notch activation in single cells while controlling cell density and ligand expression level, we show that cis-ligands can in fact activate Notch receptors. This cis-activation process resembles trans-activation in its ligand level dependence, susceptibility to cis-inhibition, and sensitivity to Fringe modification. Cis-activation occurred for multiple ligand-receptor pairs, in diverse cell types, and affected survival and differentiation in neural stem cells. Finally, mathematical modeling shows how cis-activation could potentially expand the capabilities of Notch signaling, for example enabling “negative” signaling. These results establish cis-activation as a prevalent mode of signaling in the Notch pathway, and should contribute to a more complete understanding of how Notch signaling functions in developmental, physiological, and biomedical contexts.

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