CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions
Carbonic anhydrases (CAs) are acid–base 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 GSE429...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/16/5838 |
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| author | Bor-Ren Huang Yu-Shu Liu Sheng-Wei Lai Hui-Jung Lin Ching-Kai Shen Liang-Yo Yang Dah-Yuu Lu |
| author_facet | Bor-Ren Huang Yu-Shu Liu Sheng-Wei Lai Hui-Jung Lin Ching-Kai Shen Liang-Yo Yang Dah-Yuu Lu |
| author_sort | Bor-Ren Huang |
| collection | DOAJ |
| description | Carbonic anhydrases (CAs) are acid–base 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 1α. 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. |
| first_indexed | 2024-03-10T17:26:15Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:26:15Z |
| publishDate | 2020-08-01 |
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| spelling | doaj.art-483667a0d473468b8856fda1dfa458742023-11-20T10:09:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116583810.3390/ijms21165838CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic ConditionsBor-Ren Huang0Yu-Shu Liu1Sheng-Wei Lai2Hui-Jung Lin3Ching-Kai Shen4Liang-Yo Yang5Dah-Yuu Lu6Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Basic Medical Science, China Medical University, Taichung 40402, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanDepartment of Physiology, School of Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 40402, TaiwanCarbonic anhydrases (CAs) are acid–base 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 1α. 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.https://www.mdpi.com/1422-0067/21/16/5838CAIX (carbonic anhydrase IX)hypoxic conditionGBM (glioblastoma multiforme)motilityM2 polarization |
| spellingShingle | Bor-Ren Huang Yu-Shu Liu Sheng-Wei Lai Hui-Jung Lin Ching-Kai Shen Liang-Yo Yang Dah-Yuu Lu CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions International Journal of Molecular Sciences CAIX (carbonic anhydrase IX) hypoxic condition GBM (glioblastoma multiforme) motility M2 polarization |
| title | CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions |
| title_full | CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions |
| title_fullStr | CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions |
| title_full_unstemmed | CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions |
| title_short | CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions |
| title_sort | caix regulates gbm motility and tam adhesion and polarization through egfr stat3 under hypoxic conditions |
| topic | CAIX (carbonic anhydrase IX) hypoxic condition GBM (glioblastoma multiforme) motility M2 polarization |
| url | https://www.mdpi.com/1422-0067/21/16/5838 |
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