Loss of α-1,2-mannosidase MAN1C1 promotes tumorigenesis of intrahepatic cholangiocarcinoma through enhancing CD133-FIP200 interaction

• Published in: Cell reports (Cambridge) Vol. 42; no. 12; p. 113588
• Main Authors: Wei, Yuanyan, Chen, Qihang, Chen, Jiayue, Zhou, Chenhao, Geng, Shuting, Shi, Danfang, Huang, Sijing, Liang, Zhiwei, Chen, Xiaoning, Ren, Ning, Jiang, Jianhai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.12.2023; Elsevier
• Subjects: Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - pathology; Carcinogenesis - pathology; CD133; Cell Cycle Proteins; Cell Transformation, Neoplastic - pathology; Cholangiocarcinoma - genetics; Cholangiocarcinoma - pathology; CP: Cancer; high mannose glycan; Humans; intrahepatic cholangiocarcinoma; N-glycan; tumor-initiating cell; α-1,2-mannosylation; CP: Cancer; α-1,2-mannosylation; high mannose glycan; tumor-initiating cell; N-glycan; intrahepatic cholangiocarcinoma; CD133
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113588

CD133 is widely used as a marker to isolate tumor-initiating cells in many types of cancers. The structure of N-glycan on CD133 is altered during the differentiation of tumor-initiating cells. However, the relationship between CD133 N-glycosylation and stem cell characteristics remains elusive. Here, we found that the level of α-1,2-mannosylated CD133 was associated with the level of stemness genes in intrahepatic cholangiocarcinoma (iCCA) tissues. α-1,2-mannosylated CD133+ cells possessed the characteristics of tumor-initiating cells. The loss of the Golgi α-mannosidase I coding gene MAN1C1 resulted in the formation of α-1,2-mannosylated CD133 in iCCA-initiating cells. Mechanistically, α-1,2-mannosylation promoted the cytoplasmic distribution of CD133 and enhanced the interaction between CD133 and the autophagy gene FIP200, subsequently promoting the tumorigenesis of α-1,2-mannosylated CD133+ cells. Analysis of iCCA samples showed that the level of cytoplasmic CD133 was associated with poor iCCA prognosis. Collectively, α-1,2-mannosylated CD133 is a functional marker of iCCA-initiating cells. [Display omitted] •α-1,2-mannosylated CD133 is associated with stemness in iCCA tissues•α-1,2-mannosylated CD133+ cells possess the characteristics of TICs•α-1,2-mannosylation promotes the tumorigenesis of iCCA-initiating cells•High level of α-1,2-mannosylation is associated with iCCA poor prognosis Wei et al. confirm that α-1,2-mannosylation of CD133 is a functional marker of iCCA-initiating cells. These findings provide the relationship between the N-glycan structure of CD133 and the characteristics of stem cells and provide a new strategy to eliminate iCCA-initiating cells.