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

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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MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

Cell Death and Disease ◽

10.1038/s41419-019-2023-1 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 7

Author(s):

Bin Yang ◽

Chunping Wang ◽

Hui Xie ◽

Yiwu Wang ◽

Jiagan Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Notch Signaling ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Notch Signaling Pathway ◽

Advanced Hepatocellular Carcinoma ◽

Targeted Agents ◽

Mesenchymal Transition ◽

Molecular Targeted Agents ◽

Hcc Cells

Abstract Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial–mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

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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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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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