Hypoxia: The Cornerstone of Glioblastoma

被引:116
作者
Domenech, Marta [1 ]
Hernandez, Ainhoa [1 ]
Plaja, Andrea [1 ]
Martinez-Balibrea, Eva [2 ]
Balana, Carmen [1 ]
机构
[1] Catalan Inst Oncol Badalona, BARGO Badalona Appl Res Grp Oncol, Med Oncol Dept, Badalona 08916, Spain
[2] Catalan Inst Oncol, Germans Trias & Pujol Res Inst IGTP, ProCURE Program, Badalona 08916, Spain
关键词
glioblastoma; hypoxia; HIF-1; inhibitors; INDUCIBLE FACTOR-I; CANCER STEM-CELLS; TUMOR ANGIOGENESIS; INDUCED AUTOPHAGY; GLIOMA GROWTH; HIF-1-ALPHA; EXPRESSION; FACTOR-1-ALPHA; HIF-1; TRIAL;
D O I
10.3390/ijms222212608
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glioblastoma is the most aggressive form of brain tumor in adults and is characterized by the presence of hypervascularization and necrosis, both caused by a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), the main factor activated by hypoxia, is an important driver of tumor progression in GB patients. HIF-1 alpha is a transcription factor regulated by the presence or absence of O-2. The expression of HIF-1 has been related to high-grade gliomas and aggressive tumor behavior. HIF-1 promotes tumor progression via the activation of angiogenesis, immunosuppression, and metabolic reprogramming, promoting cell invasion and survival. Moreover, in GB, HIF-1 is not solely modulated by oxygen but also by oncogenic signaling pathways, such as MAPK/ERK, p53, and PI3K/PTEN. Therefore, the inhibition of the hypoxia pathway could represent an important treatment alternative in a disease with very few therapy options. Here, we review the roles of HIF-1 in GB progression and the inhibitors that have been studied thus far, with the aim of shedding light on this devastating disease.
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页数:17
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