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Updated: Jun 11, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch-1 regulates collective breast cancer cell migration by controlling intercellular junction and cytoskeletal
Yixi Zhang1, Xiang Qin1, Ronghua Guo1
1Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Abstract:
Pathological observations show that cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration. However, general principles governing collective cell migration remain to be discovered. Different from individual cell migration, we demonstrated that the Notch-1-activation reduced collective cells speed and distances. In particular, Notch-1-activation induced cellular cytoskeletal remodelling, strengthened the intercellular junctions and cell-matrix adhesions. Mechanistically, Notch-1 activation prevented the phosphorylation of GSK-3β and the translocation of cytoplasmic free β-catenin to the nucleus, which increased E-cadherin expression and tight intercellular junctions. Moreover, Notch-1 signalling also activated the RhoA/ROCK pathway, promoting reorganization of F-actin and contractile forces produced by myosin. Further, Notch-1 activation increased cell adhesion to the extracellular substrate, which inhibited collective cell migration. These findings highlight that cell adhesions and cell-cell junctions contribute to collective cell migration and provide new insights into mechanisms of the modulation of Notch-1 signalling pathway on cancer cell malignancy.
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