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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.694141/full |
| _version_ | 1819104624680894464 |
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| author | Mengxi Xiu Mengxi Xiu Yongbo Wang Yongbo Wang Baoli Li Baoli Li Xifeng Wang Fan Xiao Fan Xiao Shoulin Chen Shoulin Chen Lieliang Zhang Lieliang Zhang Bin Zhou Bin Zhou Fuzhou Hua Fuzhou Hua |
| author_facet | Mengxi Xiu Mengxi Xiu Yongbo Wang Yongbo Wang Baoli Li Baoli Li Xifeng Wang Fan Xiao Fan Xiao Shoulin Chen Shoulin Chen Lieliang Zhang Lieliang Zhang Bin Zhou Bin Zhou Fuzhou Hua Fuzhou Hua |
| author_sort | Mengxi Xiu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T02:09:19Z |
| format | Article |
| id | doaj.art-c71fc9863b4f4625b4732ee363bd2d3e |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-22T02:09:19Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-c71fc9863b4f4625b4732ee363bd2d3e2022-12-21T18:42:26ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-06-01810.3389/fmolb.2021.694141694141The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting StrategiesMengxi Xiu0Mengxi Xiu1Yongbo Wang2Yongbo Wang3Baoli Li4Baoli Li5Xifeng Wang6Fan Xiao7Fan Xiao8Shoulin Chen9Shoulin Chen10Lieliang Zhang11Lieliang Zhang12Bin Zhou13Bin Zhou14Fuzhou Hua15Fuzhou Hua16Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, ChinaAberrant 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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.694141/fullcancerNotch3mechanismtargeted therapycancer biology |
| spellingShingle | Mengxi Xiu Mengxi Xiu Yongbo Wang Yongbo Wang Baoli Li Baoli Li Xifeng Wang Fan Xiao Fan Xiao Shoulin Chen Shoulin Chen Lieliang Zhang Lieliang Zhang Bin Zhou Bin Zhou Fuzhou Hua Fuzhou Hua The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies Frontiers in Molecular Biosciences cancer Notch3 mechanism targeted therapy cancer biology |
| 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 | cancer Notch3 mechanism targeted therapy cancer biology |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.694141/full |
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