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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Veröffentlicht in:International journal of molecular sciences 2020-08, Vol.21 (16), p.5838, Article 5838
Hauptverfasser: Huang, Bor-Ren, Liu, Yu-Shu, Lai, Sheng-Wei, Lin, Hui-Jung, Shen, Ching-Kai, Yang, Liang-Yo, Lu, Dah-Yuu
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container_title International journal of molecular sciences
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Liu, Yu-Shu
Lai, Sheng-Wei
Lin, Hui-Jung
Shen, Ching-Kai
Yang, Liang-Yo
Lu, Dah-Yuu
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 1 alpha. 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.
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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 alpha. 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.</description><identifier>ISSN: 1661-6596</identifier><identifier>ISSN: 1422-0067</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21165838</identifier><identifier>PMID: 32823915</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Acidosis ; Acids ; Adhesion ; Biochemistry &amp; Molecular Biology ; Brain cancer ; Brain Neoplasms - enzymology ; Brain Neoplasms - pathology ; Breast cancer ; CAIX (carbonic anhydrase IX) ; Cancer therapies ; Carbon dioxide ; Carbonic Anhydrase IX - metabolism ; Cell Adhesion ; Cell growth ; Cell Line, Tumor ; Cell Movement ; Cell Polarity ; Chemistry ; Chemistry, Multidisciplinary ; Chemotherapy ; Cytotoxicity ; Datasets ; Epidermal growth factor ; Epidermal growth factor receptors ; ErbB Receptors - metabolism ; GBM (glioblastoma multiforme) ; Gene expression ; Glioblastoma ; Glioblastoma - enzymology ; Glioblastoma - pathology ; Growth factors ; Humans ; Hydrogen-Ion Concentration ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-inducible factor 1a ; Hypoxia-inducible factors ; hypoxic condition ; Kinases ; Life Sciences &amp; Biomedicine ; M2 polarization ; Macrophages ; Medical prognosis ; Metabolism ; Metabolites ; Monocytes ; Monocytes - pathology ; Motility ; Pancreatic cancer ; Physical Sciences ; Physiology ; Polarization ; Protein expression ; Proteins ; Regulatory proteins ; Science &amp; Technology ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Transcription ; Tumor Hypoxia ; Tumor Microenvironment ; Tumor-Associated Macrophages - enzymology ; Tumor-Associated Macrophages - pathology ; Tumors ; Vascular endothelial growth factor</subject><ispartof>International journal of molecular sciences, 2020-08, Vol.21 (16), p.5838, Article 5838</ispartof><rights>2020. 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subjects Acidosis
Acids
Adhesion
Biochemistry & Molecular Biology
Brain cancer
Brain Neoplasms - enzymology
Brain Neoplasms - pathology
Breast cancer
CAIX (carbonic anhydrase IX)
Cancer therapies
Carbon dioxide
Carbonic Anhydrase IX - metabolism
Cell Adhesion
Cell growth
Cell Line, Tumor
Cell Movement
Cell Polarity
Chemistry
Chemistry, Multidisciplinary
Chemotherapy
Cytotoxicity
Datasets
Epidermal growth factor
Epidermal growth factor receptors
ErbB Receptors - metabolism
GBM (glioblastoma multiforme)
Gene expression
Glioblastoma
Glioblastoma - enzymology
Glioblastoma - pathology
Growth factors
Humans
Hydrogen-Ion Concentration
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Hypoxia-inducible factor 1a
Hypoxia-inducible factors
hypoxic condition
Kinases
Life Sciences & Biomedicine
M2 polarization
Macrophages
Medical prognosis
Metabolism
Metabolites
Monocytes
Monocytes - pathology
Motility
Pancreatic cancer
Physical Sciences
Physiology
Polarization
Protein expression
Proteins
Regulatory proteins
Science & Technology
Stat3 protein
STAT3 Transcription Factor - metabolism
Transcription
Tumor Hypoxia
Tumor Microenvironment
Tumor-Associated Macrophages - enzymology
Tumor-Associated Macrophages - pathology
Tumors
Vascular endothelial growth factor
title CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions
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