Hypoxia: The Cornerstone of Glioblastoma

Doménech, Marta; Hernández, Ainhoa; Plaja, Andrea; Martínez-Balibrea, Eva; Balañá, Carmen

doi:10.3390/ijms222212608

Cited by 104 publications

(72 citation statements)

References 128 publications

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“…They also exhibit the potential of self-renewal, proliferation, and multidirectional differentiation. It can be further inferred that hypoxia may be related to HIF-1α (Domènech et al, 2021). The combined inhibition of PI3K/Akt/mTOR and the Shh dual pathways and knockout or inhibition of HIF-1α can help reduce the migration ability of tumor cells and prolong the postoperative survival of patients.…”

Section: Hypoxia and Hif-1α Promote Cell Proliferationmentioning

confidence: 99%

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Wei

et al. 2022

Front. Mol. Neurosci.

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As is known to all, glioma, a global difficult problem, has a high malignant degree, high recurrence rate and poor prognosis. We analyzed and summarized signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β, TCS/mTORC1 signal pathway, JAK/STAT signal pathway, MAPK signaling pathway, the relationship between BBB and signal pathways and the mechanism of key enzymes in glioma. It is concluded that Yap1 inhibitor may become an effective target for the treatment of glioma in the near future through efforts of generation after generation. Inhibiting PI3K/Akt/mTOR, Shh, Wnt/β-Catenin, and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch cannot only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, VPS25, KCNQ1OT1, KB-1460A1.5, and CKAP4 are promising prognostic indicators and a potential therapeutic targets for glioma, meanwhile, Rheb is also a potent activator of Signaling cross-talk etc. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

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Section: Hypoxia and Hif-1α Promote Cell Proliferationmentioning

confidence: 99%

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Wei

et al. 2022

Front. Mol. Neurosci.

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“…HIF-1 is expressed in all cell types and plays a role in the cellular response to hypoxia, immune-cell adaptation, the expression of immune genes, inflammatory processes, and immunosuppression in tumours [ 49 , 50 ]. Hypoxia may impact the oviductal and uterine fluid environments [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Oviductal Oxygen Homeostasis in Patients with Uterine Myoma: Correlation between Hypoxia and Telocytes

Wrona¹,

Aleksandrovych

Bereza

et al. 2022

IJMS

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Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).

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“…It is widely accepted that HIF1α and HIF2α play partially overlapping roles in different types of cancer cells [ 22 ]. However, several reports point out the predominant role of HIF2α in pathogenic mechanisms in GCSs [ 17 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

HIF2α Upregulates the Migration Factor ODZ1 under Hypoxia in Glioblastoma Stem Cells

Carcelén

Velásquez

Vidal

et al. 2022

IJMS

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Background: Glioblastoma (GBM) remains a major clinical challenge due to its invasive capacity, resistance to treatment, and recurrence. We have previously shown that ODZ1 contributes to glioblastoma invasion and that ODZ1 mRNA levels can be upregulated by epigenetic mechanisms in response to hypoxia. Herein, we have further studied the transcriptional regulation of ODZ1 in GBM stem cells (GSCs) under hypoxic conditions and analyzed whether HIF2α has any role in this regulation. Methods: We performed the experiments in three primary GSC cell lines established from tumor specimens. GSCs were cultured under hypoxia, treated with HIF regulators (DMOG, chetomin), or transfected with specific siRNAs, and the expression levels of ODZ1 and HIF2α were analyzed. In addition, the response of the ODZ1 promoter cloned into a luciferase reporter plasmid to the activation of HIF was also studied. Results: The upregulation of both mRNA and protein levels of HIF2α under hypoxia conditions correlated with the expression of ODZ1 mRNA. Moreover, the knockdown of HIF2α by siRNAs downregulated the expression of ODZ1. We found, in the ODZ1 promoter, a HIF consensus binding site (GCGTG) 1358 bp from the transcription start site (TSS) and a HIF-like site (CCGTG) 826 bp from the TSS. Luciferase assays revealed that the stabilization of HIF by DMOG resulted in the increased activity of the ODZ1 promoter. Conclusions: Our data indicate that the HIF2α-mediated upregulation of ODZ1 helps strengthen the transcriptional control of this migration factor under hypoxia in glioblastoma stem cells. The discovery of this novel transcriptional pathway identifies new targets to develop strategies that may avoid GBM tumor invasion and recurrence.

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Hypoxia: The Cornerstone of Glioblastoma

Cited by 104 publications

References 128 publications

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Oviductal Oxygen Homeostasis in Patients with Uterine Myoma: Correlation between Hypoxia and Telocytes

HIF2α Upregulates the Migration Factor ODZ1 under Hypoxia in Glioblastoma Stem Cells

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