Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation-Reference-Cited by-同舟云学术

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation

Published:2023-12-12 Issue: Volume: Page:
ISSN:2198-3844
Container-title:Advanced Science
language:en
Short-container-title:Advanced Science

Author:

Li Huan¹,Song Chao¹,Zhang Yang¹,Liu Guohao²,Mi Hailong¹,Li Yachao¹,Chen Zhiye²,Ma Xiaoyu²,Zhang Po²,Cheng Lidong²,Peng Peng²,Zhu Hongtao²,Chen Zirong²,Dong Minhai²,Chen Sui²,Meng Hao³,Xiao QunGen²,Li Honglian¹,Wu Qiulian⁴,Wang Baofeng²,Zhang Suojun²,Shu Kai²,Wan Feng²,Guo Dongsheng²,Zhou Wenchao³,Zhou Lin¹,Mao Feng²,Rich Jeremy N.⁴⁵,Yu Xingjiang¹^ORCID

Affiliation:

1. Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

2. Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

3. Intelligent Pathology Institute The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230031 China

4. UPMC Hillman Cancer Center Department of Medicine University of Pittsburgh Medical Center Pittsburgh PA 15219 USA

5. Department of Neurology University of Pittsburgh School of Medicine Pittsburgh PA 15213 USA

Abstract

AbstractGlioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin‐binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self‐renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Funder

Natural Science Foundation of Anhui Province

Natural Science Foundation of Hubei Province

National Natural Science Foundation of China

Huazhong University of Science and Technology

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202305620

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