Open AccessFusobacterium nucleatum Promotes Colorectal Cancer Cell to Acquire Stem Cell‐Like Features by Manipulating Lipid Droplet‐Mediated Numb Degradation
Author(s) -
Liu Haiyang,
Du Junfeng,
Chao Shanshan,
Li Shuoguo,
Cai Huiyun,
Zhang Hongjie,
Chen Gang,
Liu Pingsheng,
Bu Pengcheng
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202105222
Subject(s) - fusobacterium nucleatum , numb , stem cell , microbiology and biotechnology , chemistry , cancer research , lipid droplet , cell , biology , biochemistry , genetics , porphyromonas gingivalis , bacteria
Fusobacterium nucleatum is a critical microbe that contributes to colorectal cancer progression and chemoresistance. However, whether and how F. nucleatum regulates colorectal cancer stem‐like cells (CCSCs) remains unknown. Here, the authors show that F. nucleatum promotes CCSC self‐renewal, and non‐CCSCs to acquire CCSC features by manipulating cellular lipid accumulation. F. nucleatum infection decreases lipid accumulation in CCSCs by enhancing fatty acid oxidation, thus promoting CCSC self‐renewal. In contrast, F. nucleatum increases lipid accumulation in non‐CCSCs by promoting fatty acid formation. Lipids are deposited as lipid droplets, which recruits Numb, a key cell fate regulator, through the AP2A/ACSL3 complex, and MDM2, an E3 ubiquitin ligase, though VCP and UBXD8. On lipid droplets, Numb is degraded by MDM2, activating Notch signaling, thus promoting gain of stem‐like cell features. Their findings demonstrate that F. nucleatum directly manipulates colorectal cancer cell fate and reveal the mechanism of lipid droplet‐mediated Numb degradation for activating Notch signaling.