The Interaction between DNMT1 and High‐Mannose CD133 Maintains the Slow‐Cycling State and Tumorigenic Potential of Glioma Stem Cell

Wei, Yuanyan; Chen, Qihang; Huang, Sijing; Liu, Yingchao; Li, Yinan; Yang, Xing; Shi, Danfang; Xu, Wenlong; Liu, Weitao; Ji, Zongfei; Wu, Bangwei; Chen, Xiaoning; Jiang, Jianhai

doi:10.1002/advs.202202216

Cited by 24 publications

(17 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CSCs are a small subpopulation of quiescent cells with self-renewal abilities and pluripotency that can drive tumor initiation and cause relapses [7]. CSCs generate the bulk of tumors via their self-renewal and their ability to differentiate into multiple cellular subtypes [8].…”

Section: Introductionmentioning

confidence: 99%

AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination

Zhao

Bie

et al. 2022

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Cancer stem cells (CSCs) are regarded as the "seed cells" for tumorigenesis, metastasis, recurrence and drug resistance. However, specific surface markers of CSCs of different origins have not been documented. Methods Single-cell sequencing was used to analyze the highly expressed genes in cancer stem cells of gastric cancer patients, and it was verified that AQP5 was specifically highly expressed in gastric cancer stem cells (GC-CSCs) in vivo and in vitro. The effect of AQP5-promoting LGR5 on the malignant biological function of GC-CSCs was investigated. The mechanism by which AQP5 affects GC-CSCs was explored through transcriptome sequencing, proteomic detection, mass spectrometry, etc. Results We report the identification and validation of AQP5 as a potentially specific surface marker of GC-CSCs. AQP5 was significantly upregulated in CSCs isolated from gastric cancer patients and in spheroid cells, and AQP5 was coexpressed with the canonical stem marker LGR5. Biologically, AQP5 promoted the sphere formation, proliferation, migration and invasion of GC cells in vitro and enhanced tumorigenesis in vivo. Furthermore, AQP5 coordinated with LGR5 and synergistically promoted the tumorigenesis of GC-CSCs. At the mechanistic level, AQP5 activated autophagy by inducing the LC3I/LC3II transformation in GC-CSCs, which was crucial for the biological functions of AQP5. Finally, we demonstrated that AQP5 recruited the E3 ligase TRIM21 to the key autophagy protein ULK1 and induced the K63-mediated ubiquitination of ULK1. Conclusions We elucidate a novel surface marker, AQP5, which is specifically expressed by GC-CSCs. Furthermore, our study creates a link between AQP5 and LGR5 and highlights the necessity of targeting both surface markers simultaneously as a promising approach for the treatment of gastric cancer patients.

show abstract

Section: Introductionmentioning

confidence: 99%

AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination

Zhao

Bie

et al. 2022

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…This suggests that differential N-glycosylation of CD133 extracellular domain among tumor sub-populations may be related to specific functions, subcellular localization, and turnover. In line with this, Wei et al (2022) reported that CD133 C-terminal domain interaction with DNMT1 (DNA methyltransferase 1) depends on CD133 glycosylation status in glioma stem-like cells (GSCs) [ 24 ]. High-mannose CD133 maintains GSCs in a slow-cycling state (quiescence) by blocking DNMT1 nuclear translocation.…”

Section: Cd133: Structure Localization and Posttranslational Modifica...mentioning

confidence: 98%

Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

Moreno-Londoño,

Robles-Flores

2023

Stem Cell Rev and Rep

View full text Add to dashboard Cite

CD133 protein has been one of the most used surface markers to select and identify cancer cells with stem-like features. However, its expression is not restricted to tumoral cells; it is also expressed in differentiated cells and stem/progenitor cells in various normal tissues. CD133 participates in several cellular processes, in part orchestrating signal transduction of essential pathways that frequently are dysregulated in cancer, such as PI3K/Akt signaling and the Wnt/β-catenin pathway. CD133 expression correlates with enhanced cell self-renewal, migration, invasion, and survival under stress conditions in cancer. Aside from the intrinsic cell mechanisms that regulate CD133 expression in each cellular type, extrinsic factors from the surrounding niche can also impact CD33 levels. The enhanced CD133 expression in cells can confer adaptive advantages by amplifying the activation of a specific signaling pathway in a context-dependent manner. In this review, we do not only describe the CD133 physiological functions known so far, but importantly, we analyze how the microenvironment changes impact the regulation of CD133 functions emphasizing its value as a marker of cell adaptability beyond a cancer-stem cell marker. Graphical Abstract

show abstract

“…Interestingly, the glycosyltransferase 8 domain containing 1 (GLT8D1) was recently shown to contribute to the stabilization of CD133 by interacting with it and influencing its glycosylation in glioma cells [ 157 ]. Similarly, the interaction of the high-mannose N-glycan form of CD133 with cytoplasmic DNA methyltransferase 1 (DNMT1) maintains the slow-cycling state of glioma stem cells, and favors chemotherapy resistance and tumorigenesis [ 158 ]. These observations are in line with the differential glycosylation status of CD133 in relation to cell differentiation [ 7 , 11 ].…”

Section: Molecular Biology Of Cd133mentioning

confidence: 99%

Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease

Pleskač,

Fargeas,

Veselska

et al. 2024

Cell Mol Biol Lett

View full text Add to dashboard Cite

Prominin-1 (CD133) is a cholesterol-binding membrane glycoprotein selectively associated with highly curved and prominent membrane structures. It is widely recognized as an antigenic marker of stem cells and cancer stem cells and is frequently used to isolate them from biological and clinical samples. Recent progress in understanding various aspects of CD133 biology in different cell types has revealed the involvement of CD133 in the architecture and dynamics of plasma membrane protrusions, such as microvilli and cilia, including the release of extracellular vesicles, as well as in various signaling pathways, which may be regulated in part by posttranslational modifications of CD133 and its interactions with a variety of proteins and lipids. Hence, CD133 appears to be a master regulator of cell signaling as its engagement in PI3K/Akt, Src-FAK, Wnt/β-catenin, TGF-β/Smad and MAPK/ERK pathways may explain its broad action in many cellular processes, including cell proliferation, differentiation, and migration or intercellular communication. Here, we summarize early studies on CD133, as they are essential to grasp its novel features, and describe recent evidence demonstrating that this unique molecule is involved in membrane dynamics and molecular signaling that affects various facets of tissue homeostasis and cancer development. We hope this review will provide an informative resource for future efforts to elucidate the details of CD133’s molecular function in health and disease.

show abstract

The Interaction between DNMT1 and High‐Mannose CD133 Maintains the Slow‐Cycling State and Tumorigenic Potential of Glioma Stem Cell

Cited by 24 publications

References 76 publications

AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination

AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination

Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease

Contact Info

Product

Resources

About