{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:07:29Z","timestamp":1789816049093,"version":"4.0.1"},"reference-count":75,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Science and Technology (FCT), Portugal","award":["IF\/00614\/2014"],"award-info":[{"award-number":["IF\/00614\/2014"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["IF\/00614\/2014\/CP12340006"],"award-info":[{"award-number":["IF\/00614\/2014\/CP12340006"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["UID\/BIM\/04773\/2013CBMR1334"],"award-info":[{"award-number":["UID\/BIM\/04773\/2013CBMR1334"]}]},{"name":"ERASMUS fellowship","award":["2017-1-PT01-KA103-035561"],"award-info":[{"award-number":["2017-1-PT01-KA103-035561"]}]},{"name":"Erasmus+ EU funds and the University Rouen-Normandy","award":["AMI and IDEFI REMIS financial instruments"],"award-info":[{"award-number":["AMI and IDEFI REMIS financial instruments"]}]},{"DOI":"10.13039\/501100018696","name":"Normandy Region","doi-asserted-by":"publisher","award":["810sbaAtW9"],"award-info":[{"award-number":["810sbaAtW9"]}],"id":[{"id":"10.13039\/501100018696","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Glioblastoma (GB) is the most common and deadly type of primary malignant brain tumor with an average patient survival of only 15\u201317 months. GBs typically have hypoxic regions associated with aggressiveness and chemoresistance. Using patient derived GB cells, we characterized how GB responds to hypoxia. We noted a hypoxia-dependent glycolytic switch characterized by the up-regulation of HK2, PFKFB3, PFKFB4, LDHA, PDK1, SLC2A1\/GLUT-1, CA9\/CAIX, and SLC16A3\/MCT-4. Moreover, many proangiogenic genes and proteins, including VEGFA, VEGFC, VEGFD, PGF\/PlGF, ADM, ANGPTL4, and SERPINE1\/PAI-1 were up-regulated during hypoxia. We detected the hypoxic induction of invasion proteins, including the plasminogen receptor, S100A10, and the urokinase plasminogen activator receptor, uPAR. Furthermore, we observed a hypoxia-dependent up-regulation of the autophagy genes, BNIP-3 and DDIT4 and of the multi-functional protein, NDRG1 associated with GB chemoresistance; and down-regulation of EGR1 and TFRC (Graphical abstract). Analysis of GB patient cohorts\u2019 revealed differential expression of these genes in patient samples (except SLC16A3) compared to non-neoplastic brain tissue. High expression of SLC2A1, LDHA, PDK1, PFKFB4, HK2, VEGFA, SERPINE1, TFRC, and ADM was associated with significantly lower overall survival. Together these data provide important information regarding GB response to hypoxia which could support the development of more effective treatments for GB patients.<\/jats:p>","DOI":"10.3390\/biomedicines8090310","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T08:05:18Z","timestamp":1598515518000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Investigating Glioblastoma Response to Hypoxia"],"prefix":"10.3390","volume":"8","author":[{"given":"Agathe L.","family":"Ch\u00e9deville","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-6301","authenticated-orcid":false,"given":"Anbarasu","family":"Lourdusamy","sequence":"additional","affiliation":[{"name":"Children\u2019s Brain Tumour Research Centre, School of Medicine, University of Nottingham, Biodiscovery Institute, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rita","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK"},{"name":"Centre for Biomedical Research, University of Algarve, Gambelas Campus, room 2.22, 8005-099 Faro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hill","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-3908","authenticated-orcid":false,"given":"Patricia A.","family":"Madureira","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK"},{"name":"Centre for Biomedical Research, University of Algarve, Gambelas Campus, room 2.22, 8005-099 Faro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1200\/JCO.2013.49.6968","article-title":"Dose-dense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial","volume":"31","author":"Gilbert","year":"2013","journal-title":"J. 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