Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/ijms22189845
Keywords
glioblastoma; actin polymerization; BEX1; BEX4; latrunculin B
Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [NRF-2020R1A2C2005793]
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2020M2D9A2094156]
- National Research Foundation of Korea [2020M2D9A2094156] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The study revealed the molecular mechanism underlying GBM progression after radiotherapy, showing that upregulated expression of BEX1 and BEX4 is associated with activation of the YAP/TAZ signaling pathway. Additionally, latrunculin B can inhibit GBM progression by suppressing actin polymerization.
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.
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