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

Autor: Mengxi Xiu, Yongbo Wang, Baoli Li, Xifeng Wang, Fan Xiao, Shoulin Chen, Lieliang Zhang, Bin Zhou, Fuzhou Hua
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Molecular Biosciences, Vol 8 (2021)
Druh dokumentu: article
ISSN: 2296-889X
DOI: 10.3389/fmolb.2021.694141
Popis: 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.
Databáze: Directory of Open Access Journals