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The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies

Aberrant Notch signaling profoundly affects cancer progression. Especially the Notch3 receptor was found to be dysregulated in cancer, where its expression is correlated with worse clinicopathological features and poor prognosis. The activation of Notch3 signaling is closely related to the activatio...

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Autores principales: Xiu, Mengxi, Wang, Yongbo, Li, Baoli, Wang, Xifeng, Xiao, Fan, Chen, Shoulin, Zhang, Lieliang, Zhou, Bin, Hua, Fuzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237348/
https://www.ncbi.nlm.nih.gov/pubmed/34195229
http://dx.doi.org/10.3389/fmolb.2021.694141
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author Xiu, Mengxi
Wang, Yongbo
Li, Baoli
Wang, Xifeng
Xiao, Fan
Chen, Shoulin
Zhang, Lieliang
Zhou, Bin
Hua, Fuzhou
author_facet Xiu, Mengxi
Wang, Yongbo
Li, Baoli
Wang, Xifeng
Xiao, Fan
Chen, Shoulin
Zhang, Lieliang
Zhou, Bin
Hua, Fuzhou
author_sort Xiu, Mengxi
collection PubMed
description Aberrant Notch signaling profoundly affects cancer progression. Especially the Notch3 receptor was found to be dysregulated in cancer, where its expression is correlated with worse clinicopathological features and poor prognosis. The activation of Notch3 signaling is closely related to the activation of cancer stem cells (CSCs), a small subpopulation in cancer that is responsible for cancer progression. In addition, Notch3 signaling also contributes to tumor chemoresistance against several drugs, including doxorubicin, platinum, taxane, epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) and gemcitabine, through complex mechanisms. In this review, we mainly focus on discussing the molecular mechanisms by which Notch3 modulates cancer stemness and chemoresistance, as well as other cancer behaviors including metastasis and angiogenesis. What’s more, we propose potential treatment strategies to block Notch3 signaling, such as non-coding RNAs, antibodies and antibody-drug conjugates, providing a comprehensive reference for research on precise targeted cancer therapy.
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spelling pubmed-82373482021-06-29 The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies Xiu, Mengxi Wang, Yongbo Li, Baoli Wang, Xifeng Xiao, Fan Chen, Shoulin Zhang, Lieliang Zhou, Bin Hua, Fuzhou Front Mol Biosci Molecular Biosciences Aberrant Notch signaling profoundly affects cancer progression. Especially the Notch3 receptor was found to be dysregulated in cancer, where its expression is correlated with worse clinicopathological features and poor prognosis. The activation of Notch3 signaling is closely related to the activation of cancer stem cells (CSCs), a small subpopulation in cancer that is responsible for cancer progression. In addition, Notch3 signaling also contributes to tumor chemoresistance against several drugs, including doxorubicin, platinum, taxane, epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) and gemcitabine, through complex mechanisms. In this review, we mainly focus on discussing the molecular mechanisms by which Notch3 modulates cancer stemness and chemoresistance, as well as other cancer behaviors including metastasis and angiogenesis. What’s more, we propose potential treatment strategies to block Notch3 signaling, such as non-coding RNAs, antibodies and antibody-drug conjugates, providing a comprehensive reference for research on precise targeted cancer therapy. Frontiers Media S.A. 2021-06-14 /pmc/articles/PMC8237348/ /pubmed/34195229 http://dx.doi.org/10.3389/fmolb.2021.694141 Text en Copyright © 2021 Xiu, Wang, Li, Wang, Xiao, Chen, Zhang, Zhou and Hua. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Xiu, Mengxi
Wang, Yongbo
Li, Baoli
Wang, Xifeng
Xiao, Fan
Chen, Shoulin
Zhang, Lieliang
Zhou, Bin
Hua, Fuzhou
The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
title The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
title_full The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
title_fullStr The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
title_full_unstemmed The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
title_short The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
title_sort role of notch3 signaling in cancer stemness and chemoresistance: molecular mechanisms and targeting strategies
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237348/
https://www.ncbi.nlm.nih.gov/pubmed/34195229
http://dx.doi.org/10.3389/fmolb.2021.694141
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