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CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions
- Source :
- International Journal of Molecular Sciences, Vol 21, Iss 5838, p 5838 (2020), International Journal of Molecular Sciences, Volume 21, Issue 16
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Carbonic anhydrases (CAs) are acid&ndash<br />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<br />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.
- Subjects :
- urologic and male genital diseases
Monocytes
lcsh:Chemistry
Cell Movement
Tumor-Associated Macrophages
Tumor Microenvironment
Epidermal growth factor receptor
STAT3
lcsh:QH301-705.5
Spectroscopy
GBM (glioblastoma multiforme)
Gene knockdown
biology
Brain Neoplasms
Chemistry
M2 polarization
CAIX (carbonic anhydrase IX)
Cell Polarity
General Medicine
Hydrogen-Ion Concentration
female genital diseases and pregnancy complications
Computer Science Applications
ErbB Receptors
motility
STAT3 Transcription Factor
Motility
hypoxic condition
GBM
Article
Catalysis
Inorganic Chemistry
Downregulation and upregulation
Cell Line, Tumor
Cell Adhesion
medicine
Humans
Physical and Theoretical Chemistry
Carbonic Anhydrase IX
Molecular Biology
Messenger RNA
urogenital system
Organic Chemistry
CAIX
Hypoxia-Inducible Factor 1, alpha Subunit
medicine.disease
nervous system diseases
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
biology.protein
STAT protein
Tumor Hypoxia
Glioblastoma
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 21
- Issue :
- 5838
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....3fae74ad10a88a8d642e63255d82e26d