Advanced Science (Feb 2024)
Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation
- Huan Li,
- Chao Song,
- Yang Zhang,
- Guohao Liu,
- Hailong Mi,
- Yachao Li,
- Zhiye Chen,
- Xiaoyu Ma,
- Po Zhang,
- Lidong Cheng,
- Peng Peng,
- Hongtao Zhu,
- Zirong Chen,
- Minhai Dong,
- Sui Chen,
- Hao Meng,
- QunGen Xiao,
- Honglian Li,
- Qiulian Wu,
- Baofeng Wang,
- Suojun Zhang,
- Kai Shu,
- Feng Wan,
- Dongsheng Guo,
- Wenchao Zhou,
- Lin Zhou,
- Feng Mao,
- Jeremy N. Rich,
- Xingjiang Yu
Affiliations
- Huan Li
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Chao Song
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Yang Zhang
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Guohao Liu
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Hailong Mi
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Yachao Li
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Zhiye Chen
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Xiaoyu Ma
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Po Zhang
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Lidong Cheng
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Peng Peng
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Hongtao Zhu
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Zirong Chen
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Minhai Dong
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Sui Chen
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Hao Meng
- 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
- QunGen Xiao
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Honglian Li
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Qiulian Wu
- UPMC Hillman Cancer Center Department of Medicine University of Pittsburgh Medical Center Pittsburgh PA 15219 USA
- Baofeng Wang
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Suojun Zhang
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Kai Shu
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Feng Wan
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Dongsheng Guo
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Wenchao Zhou
- 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
- Lin Zhou
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Feng Mao
- Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- Jeremy N. Rich
- UPMC Hillman Cancer Center Department of Medicine University of Pittsburgh Medical Center Pittsburgh PA 15219 USA
- Xingjiang Yu
- Department of Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
- DOI
- https://doi.org/10.1002/advs.202305620
- Journal volume & issue
-
Vol. 11,
no. 7
pp. n/a – n/a
Abstract
Abstract Glioblastoma (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.
Keywords
