scholarly journals Mathematical analysis of the effect of portal vein cells on biliary epithelial cell differentiation through the Delta-Notch signaling pathway

2021 ◽  
Author(s):  
Masaharu Yoshihara ◽  
Teppei Nishino ◽  
Manoj Kumar Yadav ◽  
Akihiro Kuno ◽  
Takeshi Nagata ◽  
...  
Keyword(s):  
Portal Vein ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Bile Ducts ◽  
Notch Signaling Pathway ◽  
Epithelial Differentiation ◽  
Synthesis Rate ◽  
Biliary Epithelial Cell ◽  
Wing Vein ◽  
Notch Receptors

Abstract Objective: The Delta-Notch signaling pathway induces the differentiation of initially homogeneous progenitor cells in many biological contexts. A mathematical modeling of this signaling pathway on Drosophila wing vein differentiation suggested the importance of synthesis rate of components of this signaling pathway. The epithelial differentiation of bile ducts in the developing liver is unique in that portal vein smooth muscle cells express extremely high amount of Delta ligands and act as a disturbance. In the present study, the importance of synthesis rate of Delta ligands and Notch receptors is mathematically examined using the model for Drosophila wing vein differentiation. Results: The epithelial differentiation was dependent on the synthesis rate of Delta ligands and Notch receptors as far as examined. This result supports the importance of synthesis rate in Delta-Notch signaling pathway components in a disturbance-dependent context as well.

scholarly journals Mathematical analysis of the effect of portal vein cells on biliary epithelial cell differentiation through the Delta-Notch signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Masaharu Yoshihara ◽  
Teppei Nishino ◽  
Manoj Kumar Yadav ◽  
Akihiro Kuno ◽  
Takeshi Nagata ◽  
...  
Keyword(s):  
Portal Vein ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Target Genes ◽  
Notch Signaling Pathway ◽  
Epithelial Differentiation ◽  
Production Rates ◽  
Fine Grained ◽  
Downstream Target ◽  
Notch Receptors

Abstract Objective The Delta-Notch signaling pathway induces fine-grained patterns of differentiation from initially homogeneous progenitor cells in many biological contexts, including Drosophila bristle formation, where mathematical modeling reportedly suggests the importance of production rate of the components of this signaling pathway. In contrast, the epithelial differentiation of bile ducts in the developing liver is unique in that it occurs around the portal vein cells, which express extremely high amounts of Delta ligands and act as a disturbance for the amount of Delta ligands in the field by affecting the expression levels of downstream target genes in the cells nearby. In the present study, we mathematically examined the dynamics of the Delta-Notch signaling pathway components in disturbance-driven biliary differentiation, using the model for fine-grained patterns of differentiation. Results A portal vein cell induced a high Notch signal in its neighboring cells, which corresponded to epithelial differentiation, depending on the production rates of Delta ligands and Notch receptors. In addition, this epithelial differentiation tended to occur in conditions where fine-grained patterning was reported to be lacking. These results highlighted the potential importance of the stability towards homogeneity determined by the production rates in Delta ligands and Notch receptors, in a disturbance-dependent epithelial differentiation.

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.

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.

Gene expression analysis of Notch signaling pathway receptors in colon cancer stem cells.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 29-29
Author(s):  
Ioannis Papasotiriou ◽  
Panagiotis Apostolou ◽  
Maria Toloudi ◽  
Marina Chatziioannou ◽  
Eleni Ioannou
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Expression Analysis ◽  
Protein Level ◽  
Gene Expression Analysis ◽  
Notch Signaling Pathway ◽  
Notch 1 ◽  
Notch 3 ◽  
Notch Receptors

29 Background: The Notch signaling pathway is not only involved in cell differentiation, but also in carcinogenesis. Four different receptors are included in this pathway (Notch-1, Notch-2, Notch-3, and Notch-4) and each is encoded by a different gene. Recent data suggest that the activation of Notch-1 induces epithelial to mesenchymal transition (EMT) consistent with cancer stem cell (CSC) phenotype. It raises therefore the question of whether there is an interaction between the receptors. The present study aims to find out the gene expression patterns of Notch receptors in Colon CSCs, under the suppression of Notch-1. Methods: The experiments were performed in Colon CSCs provided by CELPOGEN. The stemness of these cells was tested both in gene and protein level with qPCR and flow cytometry assays for the stemness markers Oct4-CD44. The gene suppressed with RNAi assays and the knockdown was evaluated with molecular biology methods. The gene expression analysis was performed after RT-qPCR assays, by using the comparative Ct method (ΔΔCt) for the calculation of relative quantitation. Results: The Colon CSCs expressed Oct4-CD44 both in gene and protein level, indicating the stemness status. The knockdown of Notch-1 up to 75%, led to a reduction of gene expression in Notch-2 and Notch-3 receptors, while no significant difference was observed in Notch-4. The Notch-2 expression was decreased up to 90% while that of Notch-3 was at the same level with Notch-1. Conclusions: This research study attempts to find out any possible correlation between the Notch receptors in Colon CSCS. The experimental data indicate that Notch-1 interacts with Notch-2 and Notch-3 by affecting heavily their gene expression. It is therefore necessary to study if the other receptors are capable for EMT and then to find out which factors are involved. Further studies to a greater range of samples need to be performed, in order to use these data at clinical level.

scholarly journals Rel/NF-κB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors

1999 ◽  
Vol 18 (10) ◽  
pp. 2803-2811 ◽  
Author(s):  
Judy Bash ◽  
Wei-Xing Zong ◽  
Satnam Banga ◽  
Amariliz Rivera ◽  
Dean W. Ballard ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Notch Receptors

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.

Regulation of EMT by Notch Signaling Pathway in Tumor Progression

2013 ◽  
Vol 13 (9) ◽  
pp. 957-962 ◽  
Author(s):  
Yumei Li ◽  
Jia Ma ◽  
Xiujuan Qian ◽  
Qiong Wu ◽  
Jun Xia ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway

Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway.

2020 ◽  
Vol 20 ◽  
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mohd Saeed ◽  
Irfan Ahmad ◽  
Irfan A. Ansari
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Mtt Assay ◽  
Annexin V ◽  
Notch Signaling Pathway ◽  
Phase Cell ◽  
Ros Generation ◽  
Notch 1

Background: Recently Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. Methods: The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4′,6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123 and Mito Tracker CMXRos staining. Scratch assay for migratory potential assessment. 7’-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1 and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated Annexin V-FITC/PI staining. Results: MTT assay demonstrated dose and time dependent cytoxicity of andrographolide on SW-480 cells. It also inhibited the migratory and colony forming potential of SW-480 cells. Furthermore, andrographolide also showed disruption of mitochondrial membrane potential and induced apoptosis through nuclear condensation. Flow cytometric evaluation showed andrographolide enhanced early and late apoptotic cells and induced upregulation of proapoptotic (Bax and Bad) and downregulation of antiapoptotic Bcl2 in treated SW-480 cells. Andrographolide augmented intracellular ROS generation and induced G0/G1 phase cell cycle arrest in colon cancer SW480 cells. Furthermore, andrographolide repressed the Notch signaling by decreasing the expression of NOTCH 1 and JAGGED 1. Conclusion: Our findings suggested that andrographolide constraint the growth of SW-480 cells through the inhibition of Notch signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document