2c931c460199ffad9a355a025d97390e ijmolsci_a2021v8n9p93.pdf 890a45df8ad5b231318c6cddeb8db5a72c074bfa ijmolsci_a2021v8n9p93.pdf 2012c2dbc38ae112f60b1401118fac89fb581fbca62f917d7b031427286f1415 ijmolsci_a2021v8n9p93.pdf Title: Hypoxia: The Cornerstone of Glioblastoma Subject: 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 is a transcription factor regulated by the presence or absence of O2. 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. Keywords: glioblastoma; hypoxia; HIF-1; HIF-1 inhibitors Author: Marta Domènech, Ainhoa Hernández, Andrea Plaja, Eva Martínez-Balibrea and Carmen Balañà Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Nov 24 02:41:26 2021 CET ModDate: Wed Nov 24 02:46:00 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 959393 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GOCQIR+EURM10 Type 1 Builtin yes yes no 10 0 NNIOJA+URWPalladioL-Ital Type 1 Custom yes yes no 14 0 EAGAFM+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 DXEOTR+URWPalladioL-Roma Type 1 Custom yes yes no 23 0 CKUQXN+CMSY10 Type 1 Builtin yes yes no 27 0 CNBEIC+VnURWPalladioL-Bold Type 1 Custom yes yes no 31 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 40 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 43 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 65 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 69 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 73 0 BFBMPO+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 95 0 BFBMPP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 101 0 BFBNBA+PalatinoLinotype CID TrueType Identity-H yes yes yes 104 0 BFBNBB+PalatinoLinotype TrueType WinAnsi yes yes no 110 0 BFBNBD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 113 0 IOLAWT+PazoMath-Italic Type 1 Builtin yes yes no 130 0 IHGURL+EURM7 Type 1 Builtin yes yes no 143 0 LMAKNS+VnURWPalladioL Type 1 Custom yes yes no 157 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-01 02:32:05 CET RepresentationInformation: ijmolsci_a2021v8n9p93.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-02-02 12:33:40 CET Size: 959393 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 570 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: What Is the Role of HIF-1? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: HIF-1 Promotes GB Aggressiveness Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Is HIF-1 the Main Promotor of Aggressiveness in Brain Tumors? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Children: Item: Title: HIF-1 Expression Is Related to the Brain Tumor’s Grade Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: HIF-1 Participates in Signaling Pathways Involved in GB Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Can We Block HIF-1 to Stop Tumor Progression? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Downregulating HIF-1 mRNA Expression Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Inhibiting HIF-1 at the Protein Level Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Promoting HIF-1 Degradation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Interfering in HIF-1 to HIF-1 HRE Binding Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Hypoxia: The Cornerstone of Glioblastoma Author: Marta Domènech, Ainhoa Hernández, Andrea Plaja, Eva Martínez-Balibrea and Carmen Balañà Subject: 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 is a transcription factor regulated by the presence or absence of O2. 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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