BEX1 and BEX4 Induce GBM Progression through Regulation of Actin Polymerization and Activation of YAP/TAZ Signaling

GBM is a high-grade cancer that originates from glial cells and has a poor prognosis. Although a combination of surgery, radiotherapy, and chemotherapy is prescribed to patients, GBM is highly resistant to therapies, and surviving cells show increased aggressiveness. In this study, we investigated t...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-09, Vol.22 (18), p.9845
Main Authors: Lee, Sungmin, Kang, Hyunkoo, Shin, Eunguk, Jeon, Jaewan, Youn, HyeSook, Youn, BuHyun
Format: Article
Language:English
Subjects:
Actin
actin polymerization
BEX1
BEX4
Brain cancer
Chemotherapy
Cytoskeleton
Gene expression
Glial cells
glioblastoma
Latrunculin B
Localization
Mechanotransduction
Medical prognosis
Morphology
Motility
Polymerization
Radiation effects
Radiation therapy
Radioresistance
Roles
Signal transduction
Xenografts
Xenotransplantation
Yes-associated protein
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Summary:GBM is a high-grade cancer that originates from glial cells and has a poor prognosis. Although a combination of surgery, radiotherapy, and chemotherapy is prescribed to patients, GBM is highly resistant to therapies, and surviving cells show increased aggressiveness. In this study, we investigated the molecular mechanism underlying GBM progression after radiotherapy by establishing a GBM orthotopic xenograft mouse model. Based on transcriptomic analysis, we found that the expression of BEX1 and BEX4 was upregulated in GBM cells surviving radiotherapy. We also found that upregulated expression of BEX1 and BEX4 was involved in the formation of the filamentous cytoskeleton and altered mechanotransduction, which resulted in the activation of the YAP/TAZ signaling pathway. BEX1- and BEX4-mediated YAP/TAZ activation enhanced the tumor formation, growth, and radioresistance of GBM cells. Additionally, latrunculin B inhibited GBM progression after radiotherapy by suppressing actin polymerization in an orthotopic xenograft mouse model. Taken together, we suggest the involvement of cytoskeleton formation in radiation-induced GBM progression and latrunculin B as a GBM radiosensitizer.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22189845