Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties
Glioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. T...
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2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Masashi Okada Yurika Nakagawa-Saito Yuta Mitobe Asuka Sugai Keita Togashi Shuhei Suzuki Chifumi Kitanaka |
| author_facet | Masashi Okada Yurika Nakagawa-Saito Yuta Mitobe Asuka Sugai Keita Togashi Shuhei Suzuki Chifumi Kitanaka |
| author_sort | Masashi Okada |
| collection | DOAJ |
| description | Glioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. The molecular mechanisms maintaining GSCs need to be elucidated in more detail for the development of GSC-targeted therapy. In comparison with patient-derived GSCs and their differentiated counterparts, we herein demonstrated for the first time that phospholipase C (PLC)ε was highly expressed in GSCs, in contrast to other PLC isoforms. A broad-spectrum PLC inhibitor suppressed the viability of GSCs, but not their stemness. Nevertheless, the knockdown of PLCε suppressed the survival of GSCs and induced cell death. The stem cell capacity of residual viable cells was also suppressed. Moreover, the survival of mice that were transplanted with PLCε knockdown-GSCs was longer than the control group. PLCε maintained the stemness of GSCs via the activation of JNK. The present study demonstrated for the first time that PLCε plays a critical role in maintaining the survival, stemness, and tumor initiation capacity of GSCs. Our study suggested that PLCε is a promising anti-GSC therapeutic target. |
| first_indexed | 2024-03-09T05:19:22Z |
| format | Article |
| id | doaj.art-9581583e40cd40a19767bed45450dfd2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:19:22Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9581583e40cd40a19767bed45450dfd22023-12-03T12:42:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315878510.3390/ijms23158785Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell PropertiesMasashi Okada0Yurika Nakagawa-Saito1Yuta Mitobe2Asuka Sugai3Keita Togashi4Shuhei Suzuki5Chifumi Kitanaka6Department of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanDepartment of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanDepartment of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanDepartment of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanDepartment of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanDepartment of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanDepartment of Molecular Cancer Science, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, JapanGlioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. The molecular mechanisms maintaining GSCs need to be elucidated in more detail for the development of GSC-targeted therapy. In comparison with patient-derived GSCs and their differentiated counterparts, we herein demonstrated for the first time that phospholipase C (PLC)ε was highly expressed in GSCs, in contrast to other PLC isoforms. A broad-spectrum PLC inhibitor suppressed the viability of GSCs, but not their stemness. Nevertheless, the knockdown of PLCε suppressed the survival of GSCs and induced cell death. The stem cell capacity of residual viable cells was also suppressed. Moreover, the survival of mice that were transplanted with PLCε knockdown-GSCs was longer than the control group. PLCε maintained the stemness of GSCs via the activation of JNK. The present study demonstrated for the first time that PLCε plays a critical role in maintaining the survival, stemness, and tumor initiation capacity of GSCs. Our study suggested that PLCε is a promising anti-GSC therapeutic target.https://www.mdpi.com/1422-0067/23/15/8785glioma initiating cellbrain tumor initiating cellphospholipase Cεc-Jun N-terminal kinase |
| spellingShingle | Masashi Okada Yurika Nakagawa-Saito Yuta Mitobe Asuka Sugai Keita Togashi Shuhei Suzuki Chifumi Kitanaka Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties International Journal of Molecular Sciences glioma initiating cell brain tumor initiating cell phospholipase Cε c-Jun N-terminal kinase |
| title | Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties |
| title_full | Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties |
| title_fullStr | Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties |
| title_full_unstemmed | Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties |
| title_short | Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties |
| title_sort | inhibition of the phospholipase cε c jun n terminal kinase axis suppresses glioma stem cell properties |
| topic | glioma initiating cell brain tumor initiating cell phospholipase Cε c-Jun N-terminal kinase |
| url | https://www.mdpi.com/1422-0067/23/15/8785 |
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