癌细胞
生物
细胞生物学
细胞内
癌症
癌症研究
遗传学
作者
Takuya Noguchi,Yuto Sekiguchi,Tatsuya Shimada,Wakana Suzuki,Takumi Yokosawa,Takatoshi Itoh,Mihoko Yamada,Midori Suzuki,Rumi Kurokawa,Yusuke Hirata,Atsushi Matsuzawa
标识
DOI:10.1073/pnas.2311282120
摘要
Liquid droplet has emerged as a flexible intracellular compartment that modulates various cellular processes. Here, we uncover an antimetastatic mechanism governed by the liquid droplets formed through liquid-liquid phase separation (LLPS) of SQSTM1/p62 and neighbor of BRCA1 gene 1 (NBR1). Some of the tyrosine kinase inhibitors (TKIs) initiated lysosomal stress response that promotes the LLPS of p62 and NBR1, resulting in the spreading of p62/NBR1 liquid droplets. Interestingly, in the p62/NBR1 liquid droplet, degradation of RAS-related C3 botulinum toxin substrate 1 was accelerated by cellular inhibitor of apoptosis protein 1, which limits cancer cell motility. Moreover, the antimetastatic activity of the TKIs was completely overridden in p62/NBR1 double knockout cells both in vitro and in vivo. Thus, our results demonstrate a function of the p62/NBR1 liquid droplet as a critical determinant of cancer cell behavior, which may provide insight into both the clinical and biological significance of LLPS.
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