{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T01:32:30Z","timestamp":1776389550223,"version":"3.51.2"},"reference-count":91,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carbonic anhydrases (CAs) are acid\u2013base regulatory proteins that modulate a variety of physiological functions. Recent findings have shown that CAIX is particularly upregulated in glioblastoma multiforme (GBM) and is associated with a poor patient outcome and survival rate. An analysis of the GSE4290 dataset of patients with gliomas showed that CAIX was highly expressed in GBM and was negatively associated with prognosis. The expression of CAIX under hypoxic conditions in GBM significantly increased in protein, mRNA, and transcriptional activity. Importantly, CAIX upregulation also regulated GBM motility, monocyte adhesion to GBM, and the polarization of tumor-associated monocytes\/macrophages (TAM). Furthermore, the overexpression of CAIX was observed in intracranial GBM cells. Additionally, epidermal growth factor receptor\/signal transducer and activator of transcription 3 regulated CAIX expression under hypoxic conditions by affecting the stability of hypoxia-inducible factor 1\u03b1. In contrast, the knockdown of CAIX dramatically abrogated the change in GBM motility and monocyte adhesion to GBM under hypoxic conditions. Our results provide a comprehensive understanding of the mechanisms of CAIX in the GBM microenvironment. Hence, novel therapeutic targets of GBM progression are possibly developed.<\/jats:p>","DOI":"10.3390\/ijms21165838","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T08:28:35Z","timestamp":1597393715000},"page":"5838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR\/STAT3 under Hypoxic Conditions"],"prefix":"10.3390","volume":"21","author":[{"given":"Bor-Ren","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Wei","family":"Lai","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Jung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Kai","family":"Shen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang-Yo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"Laboratory for Neural Repair, China Medical University Hospital, Taichung 40402, Taiwan"},{"name":"Biomedical Technology R&amp;D Center, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-5919","authenticated-orcid":false,"given":"Dah-Yuu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Photonics and Communication Engineering, Asia University, Taichung 41354, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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