https://scholars.lib.ntu.edu.tw/handle/123456789/551374
標題: | Matrix Metalloprotease-7 Mediates Nucleolar Assembly and Intra-nucleolar Cleaving p53 in Gefitinib-Resistant Cancer Stem Cells | 作者: | WEI-HSUAN YU Wu, Erxi Li, Yongqing HSIN-HAN HOU Yu, Shuan-Su C Huang, Po-Tsang WEN-HUNG KUO Qi, Dan CHONG-JEN YU |
關鍵字: | Cancer; Cell Biology; Molecular Biology | 公開日期: | 23-十月-2020 | 出版社: | CELL PRESS | 卷: | 23 | 期: | 10 | 來源出版物: | iScience | 摘要: | The enlarged distinct bulky-ball-like nucleolus matrix assembly is observed in most cancer stem cells (CSCs); however, the underlying mechanism is largely unknown. We show that matrix metalloproteinase-7 (MMP-7) shedding MUC-1 SEA domain releases MUC-1 C-ter, facilitating the nucleolus trafficking of p53 in gefitinib-resistant lung CSCs. The nucleolus colocalizations of p53, MUC-1 C-ter, MMP-7 and nucleolin were observed in the CD34+ CXADR+ CD44v3+ gefitinib-resistant EGFRL858R/T790M CSC colonies. MUC-1 C-ter induced a unique porous bulky-ball-shaped, cagelike nucleolus that functions as a nucleus molecular "garage" for potent tumor suppressor, p53. Nucleolus could also facilitate the novel sub-nucleus compartment for proteolytic processing p53 by MMP-7 to generate a 35 kDa fragment. Moreover, we show that salinomycin, an anti-CSC agent, disrupts nucleolus by inducing nucleoplasm translocation of p53 and sensitizing CSC to chemotherapy drugs. Thus, this study highlights the MMP-7-MUC-1-p53 axis in nucleolus as a potential therapeutic target for anti-CSCs to resolve the chemotherapy-resistance dilemma. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/551374 | ISSN: | 25890042 | DOI: | 10.1016/j.isci.2020.101600 |
顯示於: | 生物化學暨分子生物學科研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。