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Received: 2022-05-10

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Dianshuai GAO

Dianshuai GAO, https://orcid.org/0000-0001-8567-0238

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Journal of Zhejiang University SCIENCE B

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

Author(s):  Lin ZHANG, Yuanyuan CAO, Xiaoxiao GUO, Xiaoyu WANG, Xiao HAN, Kouminin KANWORE, Xiaoliang HONG, Han ZHOU, Dianshuai GAO

Affiliation(s):  School of Nursing, Xuzhou Medical University, Xuzhou 221004, China; more

Corresponding email(s):  gds@xzhmu.edu.cn

Key Words:  Glioblastoma; Hypoxia; Reactive oxygen species (ROS); Hypoxia-inducible factor-1α (HIF-1α); Serine protease inhibitor family E member 1 (SERPINE1)

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Lin ZHANG, Yuanyuan CAO, Xiaoxiao GUO, Xiaoyu WANG, Xiao HAN, Kouminin KANWORE, Xiaoliang HONG, Han ZHOU, Dianshuai GAO. Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma[J]. Journal of Zhejiang University Science B, 2023, 24(3): 32-49.

@article{title="Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma",
author="Lin ZHANG, Yuanyuan CAO, Xiaoxiao GUO, Xiaoyu WANG, Xiao HAN, Kouminin KANWORE, Xiaoliang HONG, Han ZHOU, Dianshuai GAO",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma
%A Yuanyuan CAO
%A Xiaoxiao GUO
%A Xiaoyu WANG
%A Xiao HAN
%A Kouminin KANWORE
%A Xiaoliang HONG
%A Dianshuai GAO
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 1
%P 32-49
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer

T1 - Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma
A1 - Lin ZHANG
A1 - Yuanyuan CAO
A1 - Xiaoxiao GUO
A1 - Xiaoyu WANG
A1 - Xiao HAN
A1 - Kouminin KANWORE
A1 - Xiaoliang HONG
A1 - Han ZHOU
A1 - Dianshuai GAO
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 1
SP - 32
EP - 49
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -

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.


张琳1,2,曹媛媛2,3,郭肖肖2,4,王潇雨2,韩笑5,Kouminin KANWORE2,洪晓亮2,周晗2,高殿帅2


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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