Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis
The Notch signaling pathway is a critical player in embryogenesis but also plays various roles in tumorigenesis, with both tumor suppressor and oncogenic activities. Mutations, deletions, amplifications, or over-expression of Notch receptors, ligands, and a growing list of downstream Notch-activated...
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doaj-d7367b4cb6fe4ba8a01dd4c3d2cfdc562021-01-08T00:03:25ZengMDPI AGCells2073-44092021-01-0110949410.3390/cells10010094Context Matters: NOTCH Signatures and Pathway in Cancer Progression and MetastasisJulia O. Misiorek0Alicja Przybyszewska-Podstawka1Joanna Kałafut2Beata Paziewska3Katarzyna Rolle4Adolfo Rivero-Müller5Matthias Nees6Department of Molecular Neurooncology, Institute of Bioorganic Chemistry Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704 Poznan, PolandDepartment of Biochemistry and Molecular Biology, Medical University in Lublin, ul. Chodzki 1, 20-093 Lublin, PolandDepartment of Biochemistry and Molecular Biology, Medical University in Lublin, ul. Chodzki 1, 20-093 Lublin, PolandDepartment of Biochemistry and Molecular Biology, Medical University in Lublin, ul. Chodzki 1, 20-093 Lublin, PolandDepartment of Molecular Neurooncology, Institute of Bioorganic Chemistry Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704 Poznan, PolandDepartment of Biochemistry and Molecular Biology, Medical University in Lublin, ul. Chodzki 1, 20-093 Lublin, PolandDepartment of Biochemistry and Molecular Biology, Medical University in Lublin, ul. Chodzki 1, 20-093 Lublin, PolandThe Notch signaling pathway is a critical player in embryogenesis but also plays various roles in tumorigenesis, with both tumor suppressor and oncogenic activities. Mutations, deletions, amplifications, or over-expression of Notch receptors, ligands, and a growing list of downstream Notch-activated genes have by now been described for most human cancer types. Yet, it often remains unclear what may be the functional impact of these changes for tumor biology, initiation, and progression, for cancer therapy, and for personalized medicine. Emerging data indicate that Notch signaling can also contribute to increased aggressive properties such as invasion, tumor heterogeneity, angiogenesis, or tumor cell dormancy within solid cancer tissues; especially in epithelial cancers, which are in the center of this review. Notch further supports the “stemness” of cancer cells and helps define the stem cell niche for their long-term survival, by integrating the interaction between cancer cells and the cells of the tumor microenvironment (TME). The complexity of Notch crosstalk with other signaling pathways and its roles in cell fate and trans-differentiation processes such as epithelial-to-mesenchymal transition (EMT) point to this pathway as a decisive player that may tip the balance between tumor suppression and promotion, differentiation and invasion. Here we not only review the literature, but also explore genomic databases with a specific focus on Notch signatures, and how they relate to different stages in tumor development. Altered Notch signaling hereby plays a key role for tumor cell survival and coping with a broad spectrum of vital issues, contributing to failed therapies, poor patient outcome, and loss of lives.https://www.mdpi.com/2073-4409/10/1/94Notch signaling pathwaytumor progressiononcogenic mutationstumor suppressor genegain and loss of function mutations (GOF and LOF)epithelial-mesenchymal transition (EMT), angiogenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia O. Misiorek Alicja Przybyszewska-Podstawka Joanna Kałafut Beata Paziewska Katarzyna Rolle Adolfo Rivero-Müller Matthias Nees |
spellingShingle |
Julia O. Misiorek Alicja Przybyszewska-Podstawka Joanna Kałafut Beata Paziewska Katarzyna Rolle Adolfo Rivero-Müller Matthias Nees Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis Cells Notch signaling pathway tumor progression oncogenic mutations tumor suppressor gene gain and loss of function mutations (GOF and LOF) epithelial-mesenchymal transition (EMT), angiogenesis |
author_facet |
Julia O. Misiorek Alicja Przybyszewska-Podstawka Joanna Kałafut Beata Paziewska Katarzyna Rolle Adolfo Rivero-Müller Matthias Nees |
author_sort |
Julia O. Misiorek |
title |
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis |
title_short |
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis |
title_full |
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis |
title_fullStr |
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis |
title_full_unstemmed |
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis |
title_sort |
context matters: notch signatures and pathway in cancer progression and metastasis |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-01-01 |
description |
The Notch signaling pathway is a critical player in embryogenesis but also plays various roles in tumorigenesis, with both tumor suppressor and oncogenic activities. Mutations, deletions, amplifications, or over-expression of Notch receptors, ligands, and a growing list of downstream Notch-activated genes have by now been described for most human cancer types. Yet, it often remains unclear what may be the functional impact of these changes for tumor biology, initiation, and progression, for cancer therapy, and for personalized medicine. Emerging data indicate that Notch signaling can also contribute to increased aggressive properties such as invasion, tumor heterogeneity, angiogenesis, or tumor cell dormancy within solid cancer tissues; especially in epithelial cancers, which are in the center of this review. Notch further supports the “stemness” of cancer cells and helps define the stem cell niche for their long-term survival, by integrating the interaction between cancer cells and the cells of the tumor microenvironment (TME). The complexity of Notch crosstalk with other signaling pathways and its roles in cell fate and trans-differentiation processes such as epithelial-to-mesenchymal transition (EMT) point to this pathway as a decisive player that may tip the balance between tumor suppression and promotion, differentiation and invasion. Here we not only review the literature, but also explore genomic databases with a specific focus on Notch signatures, and how they relate to different stages in tumor development. Altered Notch signaling hereby plays a key role for tumor cell survival and coping with a broad spectrum of vital issues, contributing to failed therapies, poor patient outcome, and loss of lives. |
topic |
Notch signaling pathway tumor progression oncogenic mutations tumor suppressor gene gain and loss of function mutations (GOF and LOF) epithelial-mesenchymal transition (EMT), angiogenesis |
url |
https://www.mdpi.com/2073-4409/10/1/94 |
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