Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma
Abstract Glioblastoma (GBM) is the most malignant tumor in brain and is highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute to the failure of conventional therapies, but the mechanisms associated with acquisition of CSC properties in GB...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05967-x |
| _version_ | 1797778611408732160 |
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| author | Eun-Jin Yun Donghwi Kim Sangwoo Kim Jer-Tsong Hsieh Seung Tae Baek |
| author_facet | Eun-Jin Yun Donghwi Kim Sangwoo Kim Jer-Tsong Hsieh Seung Tae Baek |
| author_sort | Eun-Jin Yun |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) is the most malignant tumor in brain and is highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute to the failure of conventional therapies, but the mechanisms associated with acquisition of CSC properties in GBM are not fully understood. We found that DAB2IP suppresses CSC properties by targeting the synaptic proteins neuroligin 3 (NLGN3) in GBM. Furthermore, we showed that GBM-derived NLGN3 has an oncogenic function by inducing CSC properties within GBM. Moreover, elevated NLGN3 transcription mediated by Wnt/β-catenin signaling pathway resulted in increased secretion of NLGN3 into the surrounding tumor microenvironment. Both condition media containing NLGN3 and recombinant NLGN3 transformed neighboring cells to CSCs, suggesting NLGN3 as a critical component inducing CSC properties. Furthermore, targeting NLGN3-bearing CSCs using upstream Wnt/β-catenin inhibitors synergistically enhances the efficacy of conventional treatment. Hence, we unveiled the series of regulatory mechanisms for acquisition of CSC properties in GBM progression by Wnt/β-catenin-mediated NLGN3. These results may provide a new targeting strategy to improve the therapeutic efficacy of GBM treatments. |
| first_indexed | 2024-03-12T23:19:56Z |
| format | Article |
| id | doaj.art-07b153b78bff4e7598f1b0ed3c5f83de |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-12T23:19:56Z |
| publishDate | 2023-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-07b153b78bff4e7598f1b0ed3c5f83de2023-07-16T11:29:44ZengNature Publishing GroupCell Death and Disease2041-48892023-07-0114711110.1038/s41419-023-05967-xTargeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastomaEun-Jin Yun0Donghwi Kim1Sangwoo Kim2Jer-Tsong Hsieh3Seung Tae Baek4POSTECH Biotech Center, POSTECHDepartment of Life Sciences, POSTECHDepartment of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of MedicineDepartment of Biotechnology, Kaohsiung Medical UniversityDepartment of Life Sciences, POSTECHAbstract Glioblastoma (GBM) is the most malignant tumor in brain and is highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute to the failure of conventional therapies, but the mechanisms associated with acquisition of CSC properties in GBM are not fully understood. We found that DAB2IP suppresses CSC properties by targeting the synaptic proteins neuroligin 3 (NLGN3) in GBM. Furthermore, we showed that GBM-derived NLGN3 has an oncogenic function by inducing CSC properties within GBM. Moreover, elevated NLGN3 transcription mediated by Wnt/β-catenin signaling pathway resulted in increased secretion of NLGN3 into the surrounding tumor microenvironment. Both condition media containing NLGN3 and recombinant NLGN3 transformed neighboring cells to CSCs, suggesting NLGN3 as a critical component inducing CSC properties. Furthermore, targeting NLGN3-bearing CSCs using upstream Wnt/β-catenin inhibitors synergistically enhances the efficacy of conventional treatment. Hence, we unveiled the series of regulatory mechanisms for acquisition of CSC properties in GBM progression by Wnt/β-catenin-mediated NLGN3. These results may provide a new targeting strategy to improve the therapeutic efficacy of GBM treatments.https://doi.org/10.1038/s41419-023-05967-x |
| spellingShingle | Eun-Jin Yun Donghwi Kim Sangwoo Kim Jer-Tsong Hsieh Seung Tae Baek Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma Cell Death and Disease |
| title | Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma |
| title_full | Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma |
| title_fullStr | Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma |
| title_full_unstemmed | Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma |
| title_short | Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma |
| title_sort | targeting wnt β catenin mediated upregulation of oncogenic nlgn3 suppresses cancer stem cells in glioblastoma |
| url | https://doi.org/10.1038/s41419-023-05967-x |
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