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Published VersionCC BY V4.0, Open Access
Journal article
UTP11 deficiency suppresses cancer development via nucleolar stress and ferroptosis
Redox Biology, Vol.62, pp.1-16
2023
Appears in Cancer Research Cluster Research Collection
Abstract
The eukaryotic ribosome is essential for cancer cell survival. Perturbation of ribosome biogenesis induces nucleolar stress or ribosomal stress, which restrains cancer growth, as rapidly proliferating cancer cells need more active ribosome biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and associated with poor prognoses. Interestingly, depletion of UTP11 inhibits cancer cell growth in vitro and in vivo through p53-depedednt and -independent mechanisms, whereas UTP11 overexpression promotes cancer cell growth and progression. On the one hand, the ablation of UTP11 impedes 18S rRNA biosynthesis to trigger nucleolar stress, thereby preventing MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins, RPL5 and RPL11. On the other hand, UTP11 deficiency represses the expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced levels of glutathione (GSH) and enhanced ferroptosis. Altogether, our study uncovers a critical role for UTP11 in maintaining cancer cell survival and growth, as depleting UTP11 leads to p53-dependent cancer cell growth arrest and p53-independent ferroptosis.
Details
- Title
- UTP11 deficiency suppresses cancer development via nucleolar stress and ferroptosis
- Authors
- Yu Gan (Author) - Nanchang UniversityJun Deng (Author) - First Affiliated Hospital of Nanchang UniversityQian Hao (Author) - Fudan University Shanghai Cancer CenterYingdan Huang (Author) - Fudan University Shanghai Cancer CenterTao Han (Author) - Xinxiang Medical UniversityJin-Guo Xu (Author) - Xinxiang Medical UniversityMin Zhao (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringLitong Yao (Author) - First Hospital of China Medical UniversityYingying Xu (Author) - First Hospital of China Medical UniversityJianping Xiong (Author) - First Affiliated Hospital of Nanchang UniversityHua Lu (Author) - Tulane UniversityChunmeng Wang (Corresponding Author) - Shanghai Medical College of Fudan UniversityJiaxiang Chen (Corresponding Author) - Nanchang UniversityXiang Zhou (Corresponding Author) - Fudan University Shanghai Cancer Center
- Publication details
- Redox Biology, Vol.62, pp.1-16
- Publisher
- Elsevier BV
- Date published
- 2023
- DOI
- 10.1016/j.redox.2023.102705
- ISSN
- 2213-2317
- Copyright note
- (C) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Organisation Unit
- Cancer Research Cluster; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99719552402621
- Output Type
- Journal article
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