NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM
The alteration of the cellular metabolism is a hallmark of glioma. The high glycolytic phenotype is a critical factor in the pathogenesis of high-grade glioma, including glioblastoma multiforme (GBM). GBM has been stratified into three subtypes as the proneural, mesenchymal, and classical subtypes....
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/516 |
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| author | Youngjoon Park Minwoo Park Junhyung Kim Juwon Ahn Jeongmin Sim Ji-In Bang Jinhyung Heo Hyejeong Choi Kyunggi Cho Mihye Lee Jong-Seok Moon Jaejoon Lim |
| author_facet | Youngjoon Park Minwoo Park Junhyung Kim Juwon Ahn Jeongmin Sim Ji-In Bang Jinhyung Heo Hyejeong Choi Kyunggi Cho Mihye Lee Jong-Seok Moon Jaejoon Lim |
| author_sort | Youngjoon Park |
| collection | DOAJ |
| description | The alteration of the cellular metabolism is a hallmark of glioma. The high glycolytic phenotype is a critical factor in the pathogenesis of high-grade glioma, including glioblastoma multiforme (GBM). GBM has been stratified into three subtypes as the proneural, mesenchymal, and classical subtypes. High glycolytic activity was found in mesenchymal GBM relative to proneural GBM. NADPH oxidase 2 (NOX2) has been linked to cellular metabolism and epithelial-mesenchymal transition (EMT) in tumors. The role of NOX2 in the regulation of the high glycolytic phenotype and the gain of the mesenchymal subtype in glioma remain unclear. Here, our results show that the levels of NOX2 were elevated in patients with GBM. NOX2 induces hexokinase 2 (HK2)-dependent high glycolytic activity in U87MG glioma cells. High levels of NOX2 are correlated with high levels of HK2 and glucose uptake in patients with GBM relative to benign glioma. Moreover, NOX2 increases the expression of mesenchymal-subtype-related genes, including <i>COL5A1</i> and <i>FN1</i> in U87MG glioma cells. High levels of NOX2 are correlated with high levels of COL5A1 and the accumulation of extracellular matrix (ECM) in patients with GBM relative to benign glioma. Furthermore, high levels of HK2 are correlated with high levels of COL5A1 in patients with GBM relative to benign glioma. Our results suggest that NOX2-induced high glycolytic activity contributes to the gain of the COL5A1-mediated mesenchymal phenotype in GBM. |
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| last_indexed | 2024-03-10T00:08:03Z |
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| series | Cancers |
| spelling | doaj.art-5233f42996c74ea5827b4db21ee07c7b2023-11-23T16:04:06ZengMDPI AGCancers2072-66942022-01-0114351610.3390/cancers14030516NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBMYoungjoon Park0Minwoo Park1Junhyung Kim2Juwon Ahn3Jeongmin Sim4Ji-In Bang5Jinhyung Heo6Hyejeong Choi7Kyunggi Cho8Mihye Lee9Jong-Seok Moon10Jaejoon Lim11Bundang CHA Medical Center, Department of Neurosurgery, CHA University, Yatap-dong 59, Seongnam 13496, KoreaDepartment of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, KoreaDepartment of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, KoreaBundang CHA Medical Center, Department of Neurosurgery, CHA University, Yatap-dong 59, Seongnam 13496, KoreaBundang CHA Medical Center, Department of Neurosurgery, CHA University, Yatap-dong 59, Seongnam 13496, KoreaBundang CHA Medical Center, Department of Nuclear Medicine, CHA University, Yatap-dong 59, Seongnam 13496, KoreaBundang CHA Medical Center, Department of Pathology, CHA University, Yatap-dong 59, Seongnam 13496, KoreaBundang CHA Medical Center, Department of Radiology, CHA University, Yatap-dong 59, Seongnam 13496, KoreaBundang CHA Medical Center, Department of Neurosurgery, CHA University, Yatap-dong 59, Seongnam 13496, KoreaDepartment of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, KoreaDepartment of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, KoreaBundang CHA Medical Center, Department of Neurosurgery, CHA University, Yatap-dong 59, Seongnam 13496, KoreaThe alteration of the cellular metabolism is a hallmark of glioma. The high glycolytic phenotype is a critical factor in the pathogenesis of high-grade glioma, including glioblastoma multiforme (GBM). GBM has been stratified into three subtypes as the proneural, mesenchymal, and classical subtypes. High glycolytic activity was found in mesenchymal GBM relative to proneural GBM. NADPH oxidase 2 (NOX2) has been linked to cellular metabolism and epithelial-mesenchymal transition (EMT) in tumors. The role of NOX2 in the regulation of the high glycolytic phenotype and the gain of the mesenchymal subtype in glioma remain unclear. Here, our results show that the levels of NOX2 were elevated in patients with GBM. NOX2 induces hexokinase 2 (HK2)-dependent high glycolytic activity in U87MG glioma cells. High levels of NOX2 are correlated with high levels of HK2 and glucose uptake in patients with GBM relative to benign glioma. Moreover, NOX2 increases the expression of mesenchymal-subtype-related genes, including <i>COL5A1</i> and <i>FN1</i> in U87MG glioma cells. High levels of NOX2 are correlated with high levels of COL5A1 and the accumulation of extracellular matrix (ECM) in patients with GBM relative to benign glioma. Furthermore, high levels of HK2 are correlated with high levels of COL5A1 in patients with GBM relative to benign glioma. Our results suggest that NOX2-induced high glycolytic activity contributes to the gain of the COL5A1-mediated mesenchymal phenotype in GBM.https://www.mdpi.com/2072-6694/14/3/516NOX2glycolysisCOL5A1mesenchymal phenotypeGBM |
| spellingShingle | Youngjoon Park Minwoo Park Junhyung Kim Juwon Ahn Jeongmin Sim Ji-In Bang Jinhyung Heo Hyejeong Choi Kyunggi Cho Mihye Lee Jong-Seok Moon Jaejoon Lim NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM Cancers NOX2 glycolysis COL5A1 mesenchymal phenotype GBM |
| title | NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM |
| title_full | NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM |
| title_fullStr | NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM |
| title_full_unstemmed | NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM |
| title_short | NOX2-Induced High Glycolytic Activity Contributes to the Gain of COL5A1-Mediated Mesenchymal Phenotype in GBM |
| title_sort | nox2 induced high glycolytic activity contributes to the gain of col5a1 mediated mesenchymal phenotype in gbm |
| topic | NOX2 glycolysis COL5A1 mesenchymal phenotype GBM |
| url | https://www.mdpi.com/2072-6694/14/3/516 |
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