The Role of Notch Signaling Pathway in Breast Cancer Pathogenesis

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.

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The Notch Pathway in Breast Cancer Progression

The Scientific World JOURNAL ◽

10.1155/2018/2415489 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 20

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.

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Role of Notch signaling pathway in gastric cancer pathogenesis

Współczesna Onkologia ◽

10.5114/wo.2013.33765 ◽

2013 ◽

Vol 1 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Marlena Brzozowa ◽

Łukasz Mielańczyk ◽

Marek Michalski ◽

Łukasz Malinowski ◽

Grażyna Kowalczyk-Ziomek ◽

...

Keyword(s):

Gastric Cancer ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Cancer Pathogenesis

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The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway

Current Molecular Medicine ◽

10.2174/1566524016666151123114608 ◽

2015 ◽

Vol 15 (10) ◽

pp. 980-989 ◽

Cited By ~ 17

Author(s):

Y. Kong ◽

J. Wu ◽

D. Zhang ◽

C. Wan ◽

L. Yuan

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Disease Model ◽

Notch Signaling Pathway

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Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification

Blood ◽

10.1182/blood-2011-01-328567 ◽

2011 ◽

Vol 118 (5) ◽

pp. 1264-1273 ◽

Cited By ~ 47

Author(s):

Melanie G. Cornejo ◽

Vinciane Mabialah ◽

Stephen M. Sykes ◽

Tulasi Khandan ◽

Cristina Lo Celso ◽

...

Keyword(s):

Stem Cell ◽

Notch Signaling ◽

Signaling Pathway ◽

Hematopoietic Stem Cell ◽

Stem Cell Differentiation ◽

Notch Signaling Pathway ◽

Developmental Pathways ◽

Lineage Specification ◽

Hematopoietic Stem

Abstract The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.

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Epidermoid cyst in a patient with Alagille syndrome: Coincidence or connection?

Surgical Neurology International ◽

10.25259/sni_611_2020 ◽

2020 ◽

Vol 11 ◽

pp. 432

Author(s):

Akhil Surapaneni ◽

John Kuo ◽

Min Wang ◽

Ramsey Ashour

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Epidermoid Cyst ◽

Alagille Syndrome ◽

Notch Signaling Pathway ◽

Syndrome Patient ◽

Benign Lesions ◽

Genetic Syndrome ◽

Epidermoid Cysts

Background: Alagille syndrome is a rare genetic syndrome, which arises due to defects in the Notch signaling pathway, resulting in liver, cardiopulmonary, renal, skeletal, and ophthalmologic problems, among others. Epidermoid cysts are rare congenital benign lesions that develop from ectopic ectodermal cell rests formed during neurulation. Case Description: A 24-year-old Alagille syndrome patient presented with hearing loss and was found to have a sizable posterior fossa mass. He underwent craniotomy for uneventful resection of the lesion, which was found to be an epidermoid cyst. Conclusion: While our case may represent a coincidental occurrence of two pathologies presenting together, given that epidermoid cysts arise from aberrant neurulation, and in light of the crucial role of the Notch signaling pathway both in normal neurogenesis and in the pathogenesis of Alagille syndrome, we hypothesize a possible association between these entities.

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