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VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.
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- معلومة اضافية
- المصدر:
Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
- بيانات النشر:
Original Publication: [London] : BioMed Central, 2003-
- الموضوع:
- نبذة مختصرة :
Background: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se.
Methods: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis.
Results: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis.
Conclusions: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.
(© 2024. The Author(s).)
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- Grant Information:
STINT the Swedish Foundation for Internationalisation of Higher Education and Research; CH2017-7179 the Swedish Foundation for Internationalisation of Higher Education and Research; 82273244 the National Science Foundation of China; No.7244328 Natural Science Foundation of Beijing Municipality; No.PYZ22122 the Capital Medical University Scientific Research Cultivation Fund; No.PYZ23112 the Capital Medical University Scientific Research Cultivation Fund
- Contributed Indexing:
Keywords: Glioblastoma; Mitochondria; Mitochondrial transcription factor A; Peroxisome proliferator-activated receptor gamma coactivator 1-α/PGC1α; Reactive oxygen species; Vascular endothelial growth factor receptor 2
- الرقم المعرف:
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
0 (Reactive Oxygen Species)
0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.10.1 (KDR protein, human)
- الموضوع:
Date Created: 20240503 Date Completed: 20240504 Latest Revision: 20240520
- الموضوع:
20240520
- الرقم المعرف:
PMC11067099
- الرقم المعرف:
10.1186/s12967-024-05155-1
- الرقم المعرف:
38702818
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