Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma.

Lin Zhang; Yuanyuan Cao; Xiaoxiao Guo; Xiaoyu Wang; Xiao Han; Kouminin Kanwore; Xiaoliang Hong; Han Zhou; Dianshuai Gao

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Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma.

Author: Lin ZHANG ¹ ; Yuanyuan CAO ² ; Xiaoxiao GUO ² ; Xiaoyu WANG ² ; Xiao HAN ¹ ; Kouminin KANWORE ² ; Xiaoliang HONG ² ; Han ZHOU ² ; Dianshuai GAO ³
Author Information

1. School of Nursing, Xuzhou Medical University, Xuzhou 221004, China.
2. Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou 221004, China.
3. Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou 221004, China. gds@xzhmu.edu.cn.
Publication Type:Journal Article
Keywords: Glioblastoma; Hypoxia; Hypoxia-inducible factor-1α (HIF-1α); Reactive oxygen species (ROS); Serine protease inhibitor family E member 1 (SERPINE1)
MeSH: Humans; Cell Hypoxia; Cell Line, Tumor; Glioblastoma/pathology*; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*; Plasminogen Activator Inhibitor 1/metabolism*; Reactive Oxygen Species/metabolism*; Signal Transduction; Tumor Microenvironment; Brain Neoplasms/pathology*
From: Journal of Zhejiang University. Science. B 2023;24(1):32-49
CountryChina
Language:English
Abstract: Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.