Fusobacterium nucleatum Promotes Colorectal Cancer Cell to Acquire Stem Cell-Like Features by Manipulating Lipid Droplet-Mediated Numb Degradation.
Fusobacterium nucleatum Promotes Colorectal Cancer Cell to Acquire Stem Cell-Like Features by Manipulating Lipid Droplet-Mediated Numb Degradation.
复制标题
具核梭杆菌通过操纵脂滴介导的麻木降解促进结直肠癌细胞获得干细胞样特征
DOI：
10.1002/advs.202105222
复制
发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
具核梭杆菌是导致结直肠癌进展和耐药性的关键微生物。然而，具核梭菌是否以及如何调节结直肠癌干细胞样细胞（CCSC）仍然未知。在这里，作者表明，F。nucleatum促进CCSC自我更新，非CCSC通过操纵细胞脂质积累获得CCSC特征。F.核质感染通过增强脂肪酸氧化减少CCSC中的脂质积累，从而促进CCSC自我更新。与此相反，F. nucleatum通过促进脂肪酸形成增加非CCSC中的脂质积累。脂质沉积为脂滴，其通过AP 2A/ACSL 3复合物招募Numb（一种关键细胞命运调节剂），并通过VCP和UBXD 8招募MDM 2（一种E3泛素连接酶）。在脂滴上，Numb被MDM 2降解，激活Notch信号传导，从而促进干细胞样细胞特征的获得。他们的研究结果表明，F。Nucleatum直接操纵结直肠癌细胞的命运，并揭示了脂滴介导的Numb降解激活Notch信号传导的机制。 具核梭杆菌通过促进脂肪酸形成增加非CCSC中的脂质积累。脂质沉积为脂滴，其通过AP 2A/ACSL 3复合物和MDM 2（一种E3泛素连接酶）通过VCP和UBXD 8募集Numb。在脂滴上，Numb被MDM 2降解，激活Notch信号传导，从而促进干细胞样细胞特征的获得。
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. Fusobacterium nucleatum increases lipid accumulation in non‐CCSCs by promoting fatty acid formation. Lipids are deposited as lipid droplets, which recruiting Numb 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.