Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
; (12): 32-49, 2023.
Article
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| WPRIM
| ID: wpr-971467
Biblioteca responsable:
WPRO
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.
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Texto completo:
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Índice:
WPRIM
Asunto principal:
Neoplasias Encefálicas
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Transducción de Señal
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Hipoxia de la Célula
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Especies Reactivas de Oxígeno
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Inhibidor 1 de Activador Plasminogénico
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Glioblastoma
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Línea Celular Tumoral
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Microambiente Tumoral
Límite:
Humans
Idioma:
En
Revista:
Journal of Zhejiang University. Science. B
Año:
2023
Tipo del documento:
Article