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A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles

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收录情况： ◇ SCIE

作者：
Cao Lei[1] * ; Han Ruohui[2] ; Zhao Yingying[1] ; Qin Xiaoyang[1] ; Li Qian[1] ; Xiong Hui[3] ; Kong Yu[1] ; Liu Ziyi[1] ; Li Zexing[1,4] ; Dong Feng[1] ; Li Ting[1] ; Zhao Xiujuan[1] ; Lei Lei[1] ; Zhao Qian[1] ; Liu Dayong[2] ; Wang Baofeng[5] ; Wu Xudong[1,6] ;
单位： [1]State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China. [2]Department of Endodontics and Laboratory of Stem Cells Endocrine Immunology, Tianjin Medical University School and Hospital of Stomatology, Tianjin 300070, China. [3]Department of Immunology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China [4]School of Life Sciences, Tianjin University, Tianjin 300072, China. [5]Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [6]Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
出处：
DOI： 10.1016/j.celrep.2024.114032

摘要：
N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China (32320103009, 31970579, 82103247, and 31701126), the National Key Research and Development Project of Stem Cell and Transformation Research (2019YFA0112100), the Key Research Project of Tianjin Education Commission (2020ZD13), the national youth talent support program, Tianjin Medical University Talent Excellence Program, and Tianjin Postgraduate Research Innovation Project (2021YJSB273, 2021YJSB274).
语种：
外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
JCR分区：
出版当年[2022]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China.
通讯作者：
通讯机构： [1]State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China. [6]Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
推荐引用方式(GB/T 7714)：
Cao Lei,Han Ruohui,Zhao Yingying,et al.A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles[J].Cell Reports.2024,43(4):114032.doi:10.1016/j.celrep.2024.114032.
APA：
Cao Lei,Han Ruohui,Zhao Yingying,Qin Xiaoyang,Li Qian...&Wu Xudong.(2024).A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles.Cell Reports,43,(4)
MLA：
Cao Lei,et al."A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles".Cell Reports 43..4(2024):114032

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