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

  • Adv Sci (Weinh). 2023 Dec 12:e2305620. doi: 10.1002/advs.202305620.
Huan Li  1 ,  Chao Song  1 ,  Yang Zhang  1 ,  Guohao Liu  2 ,  Hailong Mi  1 ,  Yachao Li  1 ,  Zhiye Chen  2 ,  Xiaoyu Ma  2 ,  Po Zhang  2 ,  Lidong Cheng  2 ,  Peng Peng  2 ,  Hongtao Zhu  2 ,  Zirong Chen  2 ,  Minhai Dong  2 ,  Sui Chen  2 ,  Hao Meng  3 ,  QunGen Xiao  2 ,  Honglian Li  1 ,  Qiulian Wu  4 ,  Baofeng Wang  2 ,  Suojun Zhang  2 ,  Kai Shu  2 ,  Feng Wan  2 ,  Dongsheng Guo  2 ,  Wenchao Zhou  3 ,  Lin Zhou  1 ,  Feng Mao  2 ,  Jeremy N Rich  4  5 ,  Xingjiang Yu  1
Affiliations
  • 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.
PMID: 38087889 DOI: 10.1002/advs.202305620
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
HDAC2; HIF1α Hypoxia; glioblastoma stem cells; natural borneol; sodium valproate; transgelin.
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