Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting
| العنوان: | Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting |
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| المؤلفون: | Chong Liu, Jin Li, Simon Hippenmeyer, Baizhou Li, Wenhong Jiang, Yan Wang, Wei Wang, Jianmin Zhang, Qingqing Gao, Pengxiang Chen, Minmin Yang, Qinghui Liang, Rui Liu, Lisha Wang, Rui Jing, Lili Bao, Biying Qiu, Yu Shi, Chengwei Cai, Xiu-Wu Bian, Ying-Jie Wang, Junming Zhu, Jianghong Man, Fangjie Shao, Bo Kang, Anhao Tian |
| المصدر: | Advanced Science Advanced Science, Vol 7, Iss 21, Pp n/a-n/a (2020) |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | neural stem cells (NSCs), General Chemical Engineering, medicine.medical_treatment, Cell, General Physics and Astronomy, Medicine (miscellaneous), 02 engineering and technology, Biology, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), cancer cell of origin, lineage tracing, IGF1R, Glioma, glioma, medicine, General Materials Science, lcsh:Science, Insulin-like growth factor 1 receptor, Mutation, Full Paper, Cell growth, Growth factor, mosaic analysis with double markers (MADM), General Engineering, Full Papers, 021001 nanoscience & nanotechnology, medicine.disease, Neural stem cell, 0104 chemical sciences, 3. Good health, body regions, stomatognathic diseases, medicine.anatomical_structure, nervous system, Cancer cell, oligodendrocyte precursor cells (OPCs), Cancer research, lcsh:Q, 0210 nano-technology |
| الوصف: | Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma. Using genetic mouse models with NSCs or OPCs as the glioma cells‐of‐origin/mutation, it is shown that desirable outcomes of IGF1R knockout on cell growth require mutant cells with the development hierarchy to commit to the OPC identity. The findings herein identify the cellular window of IGF1R targeting, and firmly establish IGF1R as an effective target for glioma prevention and treatment. |
| اللغة: | English |
| تدمد: | 2198-3844 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7727a143c543d8c4800c2adbb2c91da0 http://europepmc.org/articles/PMC7610337 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7727a143c543d8c4800c2adbb2c91da0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21983844 |
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