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Notch and its oncogenic activity in human malignancies
BACKGROUND: Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in differ...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Vienna
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653712/ https://www.ncbi.nlm.nih.gov/pubmed/29104587 http://dx.doi.org/10.1007/s10353-017-0491-z |
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author | Brzozowa-Zasada, Marlena Piecuch, Adam Michalski, Marek Segiet, Oliwia Kurek, Józef Harabin-Słowińska, Marzena Wojnicz, Romuald |
author_facet | Brzozowa-Zasada, Marlena Piecuch, Adam Michalski, Marek Segiet, Oliwia Kurek, Józef Harabin-Słowińska, Marzena Wojnicz, Romuald |
author_sort | Brzozowa-Zasada, Marlena |
collection | PubMed |
description | BACKGROUND: Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown. METHODS: This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis. RESULTS: Numerous reports have indicated that alterations in Notch signaling and its oncogenic activity were originally associated with the pathogenesis of T‑cell acute lymphoblastic leukemia/lymphoma (T-ALL), an aggressive hematologic tumor affecting children and adolescents. The possibility that Notch could play a significant role in human breast cancer development comes from studies on mouse mammary tumor virus-induced cancer. Numerous findings over the past several years have indicated that alterations in Notch signaling are also responsible for ovarian cancer development. Mention should also be made of the connection between expression of Notch 3 and increased resistance to chemotherapy, which remains a major obstacle to successful treatment. Notch as an oncogenic factor is also involved in the development of colon cancer, lung carcinoma and Kaposi’s sarcoma. CONCLUSION: Notch is a binary cell fate determinant and its overexpression has been described as oncogenic in a wide array of human malignancies. This finding led to interest in therapeutically targeting this pathway, especially by the use of gamma-secretase inhibitors (GSIs) blocking the cleavage of Notch receptors at the cell membrane by the inhibition of Notch intracellular domain (NICD) releasing. Preclinical cancer models have revealed that GSIs suppress the growth of cancers such as pancreatic, breast and lung cancer. |
format | Online Article Text |
id | pubmed-5653712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer Vienna |
record_format | MEDLINE/PubMed |
spelling | pubmed-56537122017-11-01 Notch and its oncogenic activity in human malignancies Brzozowa-Zasada, Marlena Piecuch, Adam Michalski, Marek Segiet, Oliwia Kurek, Józef Harabin-Słowińska, Marzena Wojnicz, Romuald Eur Surg Review BACKGROUND: Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown. METHODS: This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis. RESULTS: Numerous reports have indicated that alterations in Notch signaling and its oncogenic activity were originally associated with the pathogenesis of T‑cell acute lymphoblastic leukemia/lymphoma (T-ALL), an aggressive hematologic tumor affecting children and adolescents. The possibility that Notch could play a significant role in human breast cancer development comes from studies on mouse mammary tumor virus-induced cancer. Numerous findings over the past several years have indicated that alterations in Notch signaling are also responsible for ovarian cancer development. Mention should also be made of the connection between expression of Notch 3 and increased resistance to chemotherapy, which remains a major obstacle to successful treatment. Notch as an oncogenic factor is also involved in the development of colon cancer, lung carcinoma and Kaposi’s sarcoma. CONCLUSION: Notch is a binary cell fate determinant and its overexpression has been described as oncogenic in a wide array of human malignancies. This finding led to interest in therapeutically targeting this pathway, especially by the use of gamma-secretase inhibitors (GSIs) blocking the cleavage of Notch receptors at the cell membrane by the inhibition of Notch intracellular domain (NICD) releasing. Preclinical cancer models have revealed that GSIs suppress the growth of cancers such as pancreatic, breast and lung cancer. Springer Vienna 2017-09-18 2017 /pmc/articles/PMC5653712/ /pubmed/29104587 http://dx.doi.org/10.1007/s10353-017-0491-z Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Brzozowa-Zasada, Marlena Piecuch, Adam Michalski, Marek Segiet, Oliwia Kurek, Józef Harabin-Słowińska, Marzena Wojnicz, Romuald Notch and its oncogenic activity in human malignancies |
title | Notch and its oncogenic activity in human malignancies |
title_full | Notch and its oncogenic activity in human malignancies |
title_fullStr | Notch and its oncogenic activity in human malignancies |
title_full_unstemmed | Notch and its oncogenic activity in human malignancies |
title_short | Notch and its oncogenic activity in human malignancies |
title_sort | notch and its oncogenic activity in human malignancies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653712/ https://www.ncbi.nlm.nih.gov/pubmed/29104587 http://dx.doi.org/10.1007/s10353-017-0491-z |
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