Role of Notch signaling pathway in gastric cancer pathogenesis

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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The Carcinogenic Role of the Notch Signaling Pathway in the Development of Hepatocellular Carcinoma

Journal of Cancer ◽

10.7150/jca.26847 ◽

2019 ◽

Vol 10 (6) ◽

pp. 1570-1579 ◽

Cited By ~ 14

Author(s):

Qinfeng Huang ◽

Junhong Li ◽

Jinghui Zheng ◽

Ailing Wei

Keyword(s):

Hepatocellular Carcinoma ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway

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SPON2 Is Upregulated through Notch Signaling Pathway and Promotes Tumor Progression in Gastric Cancer

Cancers ◽

10.3390/cancers12061439 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1439

Author(s):

Hyeon-Gu Kang ◽

Won-Jin Kim ◽

Myung-Giun Noh ◽

Kyung-Hee Chun ◽

Seok-Jun Kim

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Notch Signaling ◽

Signaling Pathway ◽

Cancer Progression ◽

Notch Signaling Pathway ◽

Migration And Invasion ◽

Gene Assay ◽

Gastric Cancer Progression

Spondin-2 (SPON2) is involved in cancer progression and metastasis of many tumors; however, its role and underlying mechanism in gastric cancer are still obscure. In this study, we investigated the role of SPON2 and related signaling pathway in gastric cancer progression and metastasis. SPON2 expression levels were found to be upregulated in gastric cancer cell lines and patient tissues compared to normal gastric epithelial cells and normal controls. Furthermore, SPON2 silencing was observed to decrease cell proliferation and motility and reduce tumor growth in xenograft mice. Conversely, SPON2 overexpression was found to increase cell proliferation and motility. Subsequently, we focused on regulatory mechanism of SPON2 in gastric cancer. cDNA microarray and in vitro study showed that Notch signaling is significantly correlated to SPON2 expression. Therefore, we confirmed how Notch signaling pathway regulate SPON2 expression using Notch signaling-related transcription factor interaction and reporter gene assay. Additionally, activation of Notch signaling was observed to increase cell proliferation, migration, and invasion through SPON2 expression. Our study demonstrated that Notch signaling-mediated SPON2 upregulation is associated with aggressive progression of gastric cancer. In conclusion, we suggest upregulated SPON2 via Notch signaling as a potential target gene to inhibit gastric cancer progression.

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Non-small-cell lung carcinoma: role of the Notch signaling pathway

Lung Cancer Targets and Therapy ◽

10.2147/lctt.s60329 ◽

2015 ◽

pp. 43 ◽

Cited By ~ 1

Author(s):

Maurizio Bocchetta ◽

Levi Barse

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Notch Signaling Pathway ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma

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A role of the LIN-12/Notch signaling pathway in diversifying the non-striated egg-laying muscles in C. elegans

Developmental Biology ◽

10.1016/j.ydbio.2014.02.001 ◽

2014 ◽

Vol 389 (2) ◽

pp. 137-148 ◽

Cited By ~ 6

Author(s):

Jared J. Hale ◽

Nirav M. Amin ◽

Carolyn George ◽

Zachary Via ◽

Herong Shi ◽

...

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Egg Laying ◽

C Elegans

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Association between Notch signaling pathway and cancer

Acta medica Lituanica ◽

10.6001/actamedica.v19i4.2553 ◽

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.

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